摘要
神经生长因子(NGF)是一种对神经细胞起营养作用的多肽分子，在神经元的生长发育、轴突的生长、递质的合成及细胞的凋亡等阶段起着重要作用，是人和动物体内必不可少的多功能因子。它与多种疾病的发生、发展有关,且无论是它本身水平的改变或是它的受体水平或功能的改变都对某些疾病的病理生理学具有重要影响。多项研究证实，NGF对神经退行性疾病，糖尿病性神经病，神经损伤,炎症和某些癌症具有潜在治疗作用。但作为制剂，NGF的药代动力学差，分子质量较大，半寿期短；不稳定，不易跨越血脑屏障；另外，NGF有两个能执行相反作用的受体Trk A和p75~(NTR)，能激活多个信号通路，产生不同的反应；再加上其较高的价格，使NGF很难大规模应用于神经退行性疾病、糖尿病性神经病及神经损伤等的临床治疗。因此，人们以寻找具有类似NGF活性的，或是能促进NGF在细胞内合成分泌的，或是具有NGF激动剂或拮抗剂活性的药代动力学高，副作用少的小分子化合物作为解决这一难题的有效途径。
为了寻找具有促神经分化活性的小分子，本文以大鼠嗜铬细胞瘤细胞系PC12(ratpheochromocytoma cells)作为研究模型，在细胞形态观察、细胞分化率分析的基础上，对鳞盖肉齿菌Sarcodon scabrosus (Fr.) karst子实体中分离得到的一系列化合物进行了活性筛选，选择结构相似的鸟巢烷型二萜类化合物和两种原小檗碱类化合物及其氢化产物作为研究对象，采用形态观察、细胞计数、ELISA，Western blotting等方法对其构效关系及分子机理进行了系统研究。获得了以下主要创新性结果：
1.本文首次对20个小分子化合物(包括6个新化合物和一个人工合成的化合物)对NGF诱导的PC12细胞轴突生长的作用进行了研究，首次发现sarcodonin G和sarcodonin A具有NGF依赖的促PC12细胞轴突生长活性。通过对PC12细胞p-TrkA和p-ERK的检测、形态学统计分析以及化合物的结构分析，发现多个官能团对鸟巢烷型二萜类化合物的NGF依赖的促PC12轴突生长活性有重要影响，从分子水平阐明化合物构效关系。同时本文还证明sarcodonin G和sarcodonin A都是通过NGF/Trk A体系触发反应，并经由ERK1/2信号转导通路促进NGF依赖的PC12细胞轴突生长。本文以活性先导化合物的发现为基础，为鳞盖肉齿菌的开发利用提供了实验依据；为设计具有临床应用价值的神经营养因子激动剂提供了理论依据。
2.本文首次发现一个新化合物scabronine M具有抑制NGF诱导的PC12细胞轴突生长的活性，且该化合物是通过NGF/Trk A体系触发反应，部分影响ERK1/2途径，实现对NGF依赖的PC12细胞轴突生长的剂量依赖性抑制作用。本文以活性先导化合物的发现为基础，为鳞盖肉齿菌的开发利用提供了实验依据；为设计具有临床应用价值的神经营养因子抑制剂提供了理论依据。
3.本文首次对两种植物源原小檗碱类化合物小檗碱和巴马汀的氢化产物——四氢小檗碱和四氢巴马汀的NGF诱导的PC12细胞轴突生长的作用进行了研究，首次发现四氢小檗碱和四氢巴马汀具有促NGF依赖的PC12细胞轴突生长活性。通过同一浓度下四种化合物分别对PC12细胞p-Trk A和p-ERK作用的比较，发现氢化修饰能显著提高原小檗碱类化合物的生物学活性。本文为含有小檗碱成分的植物的有效利用及新药开发提供理论基础。
Nerve growth factor (NGF), a neurotrophic polypeptide, is an indispensable pleiotrophicfactor in human and animals. NGF plays a crucial role in neuronal survival, differentiation,growth, axon growth, neuro-transmitter synthesis and cell apoptosis. The potential of NGF asa therapeutic agent for several diseases including neurodegenerative disorders, diabeticneuropathy, nerve injury, inflammation and certain types of cancers has been indicated byseveral investigators. It involves with the genesis and development of a variety of diseases,and the changes in level of NGF itself or the receptor and in their functions have an importantinfluence on the pathophysiology of certain diseases. Despite the amazing therapeuticpotential, NGF is not considered an ideal drug candidate. In fact, they show a poorpharmacokinetic behavior, short half-lives, instability in vivo, unable to cross the blood-brainbarrier to reach target tissues. And NGF binds two receptors (Trks and p75~(NTR)) which cancommand opposite actions, activate various signal pathways and produce different responses.Moreover, the NGF protein is relatively expensive to produce for medicinal applications, so itis difficult to large-scale application in neurodegenerative diseases, diabetic neuropathy andnerve injury. Therefore, efforts have been devoted to search for NGF mimics, NGF inducor orNGF agonist/antagonist activity compound with small molecule, better pharmacokinetics andless side effects.
In order to find small molecules that can promote neuronal differentiation, we detectedthe NGF-dependent neurite outgrowth activity of a series of compounds isolated from thefruiting bodies of Sarcodon scabrosus (Fr.) karst, using PC-12cells as model. On the basis ofmorphological observation and statistical analysis of the cell differentiation, we chosecyathane-type diterpenoids and two protoberberines and their hydrogenation products asobject to study. Through morphological observation, cell counting, ELISA, Western blotting,we studied the structure-activity relationships and explained the differences on a molecularlevel. The main results were as follows：
1. This is the first time to detect the NGF-induced PC12cell neurite outgrowth of20smallmolecules (including six new compounds and a synthetic compound). We reported firstlysarcodonin G and sarcodonin A have the NGF-dependent neurite outgrowth-promotingactivity in vitro. On the basis of the biological results such as detection of p-Trk A and p-ERK, statistics results of cell morphology and the structure of compounds, we initiallyclarified the structure-activity relationship on a molecular and mechanistic level and foundsome functional groups important for the NGF-dependent neurite outgrowth-promotingactivity. At the same time, we also confirmed they promoted the NGF-induced neuriteoutgrowth through NGF/Trk A and ERK1/2MAPK signal pathway in does-dependentmanner. The results provided the experimental base for further utilization of themushroom Sarcodon scabrosus (Fr.) karst and theoretical foundation for design of NGFagonist on the basis of discovery of bioactive lead compounds.2. We reported firstly scabronine M, a new compound has a suppressive effect onNGF-induced neuronal differentiation in vitro. We confirmed that it interacted with Trk A,partilly influenced the ERK1/2MAPK pathway to suppress the cell differentiationprocesses. The results provided the experimental base for further utilization of themushroom Sarcodon scabrosus (Fr.) karst and theoretical foundation for design of NGFagonist on the basis of discovery of bioactive lead compounds.3. We firstly reported tetrahydroberberine and tetrahydropalmatine, two hydrogenationproducts of plant origin protoberberines: bererine and palmatine, have the NGF-dependentneurite outgrowth-promoting activity in vitro. We compared the NGF-dependent neuriteoutgrowth-promoting activity of these four compounds through the lever of p-Trk A andp-ERK, and concluded that derivatives had better activity than their parent compoundsrespectively, the hydrogenation of protoberberines had a significant effect on their activity.The results provided a theoretical basis for the effective use of berberine-containing plantsand development of new drugs.
引文
陈青,奉文尚,何峰,钟翎.2009.原小檗碱类多靶点抗老年性痴呆症药理作用.中山大学学报(自然科学版),48(5):86~90
杜建厂,王兴娜,谭仁祥,刘吉开.2006.担子菌亮光钹菌化学成分的研究.中草药,37(9):1297~1300
高锦明,董泽军,刘吉开.2000.蓝黄红菇的化学成分.云南植物研究,22(1):85~89
卯晓岚.2000.中国大型真菌:河南科学技术出版社,郑州:420~422和246~247
李波,朱维良,曾步兵,陈凯先.原小檗碱类化合物合成研究的新进展.中国药学杂志,201146(1):1~6
李冬梅,孙慧萍,阎赋琴.2008.神经生长因子药效学研究.中国实验动物学报,16(2):150~152
刘吉开.2007.高等真菌化学成分及其生物活性的研究.中国科学基金,21(2):69~70
刘吉开,胡琳,丁智慧,高锦明,董泽军,谭建文.2003.高等真菌次生代谢产物及其生物活性.中草药,34(1):84~86
刘卫涛.2008.小檗碱衍生物的制备及其神经营养活性研究.[硕士学位论文].陕西杨凌.西北农林科技大学:24~25
刘宇鹏,赵德伟,吕德成,崔旭,王卫明,孙强.2006.神经生长因子在大鼠骨折部位的表达.中国临床康复,17:107~109
潘树义,刘大庸,余磊,王苏平,钟世镇.2000.人参皂甙对NGF引导的鼠胚脊髓神经节细胞轴突生长的影响.中国神经科学杂志,4:13~15
石庆秋,张学荣.2008.蛇毒神经生长因子基因表达系统的探讨.蛇志,20(1):46~50
王向鹏,杨智勇,王廷华,王进昆.2006.神经生长因子和脑源性神经营养因子在脑胶质瘤内的表达.国际神经病学神经外科学杂志,2:99~102
王兴娜,杜建厂,谭仁祥,刘吉开.2005.担子菌黄卷缘齿菌的化学成分.中草药,36(8):1126~1130
韦传宝.2007.蛇毒神经生长因子的应用研究进展.实用医学杂志,23(13):2016~2018
王刚,宋韶鸣,周晓玉,吴玉新,何俊平,贺利祯,耿昌平.2006.新生儿产时颅脑损伤56例治疗探讨.中国新生儿科杂志,6:358~359
王志红.2004.盐酸小檗碱对HL-60细胞增殖与分化的影响.中国药理学通报,20(11):1305~1312
汪家政,吴卫平,柳川,李玉书,鲍忠祈.1991.神经元营养因子对大鼠隔-海马通路损伤的影响.中国应用生理学杂志,3:13~15
俞诗源,刘忠虎,王子仁.2002.神经生长因子.西北师范大学学报（自然科学版）,38(3):106~111
朱锦琪，冯俊涛，胡成平,汤渝玲,林敏娟,罗百灵．2006.神经生长因子、白血病抑制因子调控支气管哮喘大鼠神经源性炎症机制的研究．中华结核和呼吸杂志,6:376~380
张志坚,朱小敏,邱雪立.2007.下肢长干骨骨折应用带锁髓内钉术后并发症的防治.实用医技杂志,14(9):1179~1180
张素,陈崇宏,郑志.2003.神经生长因子的研究.海峡药学,15(2):8~10
Aloe L，Calza L.2004. NGF and related molecules in health and diseases. Progress in brain research,146:111~126
Aloyz R S, Bamji S X, Pozniak C D, Toma J G, Atwal J, Kaplan D R, Miller F D.1998. p53is essential fordevelopmental neuron death as regulated by the TrkA and p75neurotrophin receptors. J Cell Biol,143:1691~1703
Angus W G R and Contreras M L.1996. Effects of Polychlorinated Biphenyls on Dopamine Release fromPC12Cells. Toxicology Letters,89(3):191~199
Apfel S C.2002. Nerve growth factor for the treatment of diabetic neuropathy：what went wrong, whatwent right，and what does the future hold?. Int Rev Neurobiol,50:393~413
Arevalo C, de Miguel R, Hernandez-Tristan R.2001. Cannabinoid effects on anxiety-related behavioursand hypothalamic neurotransmitters. Pharmacol Biochem Behav,70:123~131
Atsutoshi H, Yoshitaka O, Kyoko O M, Yuji T, Ken K, Toshiya Y, Takeshi N, Hidefumi W, Kazunori Y,Masanobu M.2007. Direct in vivo protein transduction into cardiomyocytes of rats. AutonomicNeuroscience,135(1):115~116
Ayer W, Taube H.1973. Metabolites of Cyathus helenae A new class of diterpenoids. Can J Chem,51(23):3842~384
Bachis A，Rabin SJ，Del Fiacco M，Mocchetti I.2002. Gangliosides prevent excitotoxicitythroughactivation of TrkB receptor. Neurotox Res,4(3):225~234
Bandtlow C，Dechant G.2004. From cell death to neuronal regeneration, effects of the p75neurotrophinreceptor depend on interactions with partner subunits. Sci STKE,235:24
Barde Y A.1989. Trophic factors and neuronal survival. Neuron,2(6):1525~1534
Barde Y A, Edgar H, Thoenen H.1982. Purification of a new neurotrophic factor from mammalian brain.EMBO J,1:549~553
Bartus R T，Dean R L，Beer B and Lippa A S.1982. The cholinergic hypothesis of geriatric memorydysfunction. Science,217:408~414
Bassili M, Birman E，Schor N F and Saragovi H U.2010. Differential roles of Trk and p75neurotrophinreceptors in tumorigenesis and chemoresistance ex vivo and in vivo. Cancer Chemother Pharmacol,65(6):1047~1056
Beáta T r csik, József Szeberényi.2000. Anisomycin Affects Both Pro-and Antiapoptotic Mechanisms inPC12Cells. Biochemical and Biophysical Research Communications,278:550~556
Bentley C A and Lee K F.2000. P75is important for axon growth and schwann cell migration duringdevelopment. J.Neurosci,20:7706~7715
Berkemeier L R, Winslow J W, Kaplan D R, Nikolics K, Goeddel D V, Rosenthal A.1991. Neurotrophin-5:a novel neurotrophic factor that activates trk and trk B. Neuron,7:857~866
Bernd P, Miles K, Rozenberg I, Borghjid S, Kirby M L.2004. Neurotrophin-3and TrkC are expressed inthe outflow tract of the developing chicken heart. Dev Dyn,230:767~772
Berninger B and Poo M.1999. Neurobiology: Exciting neurotrophins. Nature,401(6756):862~863
Bilderback T R, Gazula V R, Lisanti M P, Dobrowsky R T.1999. Caveolin interacts with Trk A and p75(NTR) and regulates neurotrophin signaling pathways. J Biol Chem,274:257~263
Birnbaum T, Roider J, Schankin C J, Padovan C S, Schichor C, Goldbrunner R, Straube A.2007.Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines. JNeurooncol,83:241~247
Bonini S, Lambiase A, Bonini S, Angelucci F, Magrini L, Manni L, Aloe L.1996. Circulating nervegrowth factor levels are increased in human s with allergic diseases and asthma．Proc Natl Acad SciUSA,93(20):10955~10960
Bowen M.1976. Theory in the practice of psychotherapy. In P. Guerin (Ed.).Family therapy: Theory andpractice, New York: Gardner Press.42~90
Bradshaw R A, Murray-Rust J, Ibá ez C F, McDonald N Q, Lapatto R and Blundell T L.1994. Nervegrowth factor: Structure/function relationships. Protein Science,3:1901~1913
Brann A B，Tcherpakov M，Williams I M，Futerman A H and Fainzilber M.2002. Nerve growthfactor-induced p75-mediated death of cultured hippocampal neurons is age-dependent and transducedthrough ceramide generated by neutral sphingomyelinase. J Biol Chem,277:9812~9818
Braun L，Ohayon H and Cossart P.1998. The InlB protein of Listeria monocytogenes is sufficient topromote entry into mammalian cells. Mol Microbiol,27:1077~1087
Bredesen D E, Mehlen P, Rabizadeh S.2004. Apoptosis and dependence receptors: a molecular basis forcellular addiction. Physiol Rev,84:411~430
Bronfman F C and Fainzilber M.2004. Multi-tasking by the p75receptor: sortilin things out?. EMBOReports,5:867~871
Bruno M A, Clarke P B, Seltzer A, Quirion R, Burgess K, Cuello C A and Saragovi H U.2004.Long-lasting rescue of age-associated deficits in cognition ard the CNS cholinergic phenotype by apartial agonist peptidomimetic ligand of TrkA. J Neurosci,24:8009~8018
Buday L and Downward J.1993. Epidermal growth factor regulates p21ra' through the formation of acomplex of receptor, Grb2adapter protein, and Sos nucleotide exchange factor. Cell,73:611~620
Calatozzolo C, Salmaggi C, Pollo B, Sciacca F L, Lorenzetti M, Franzini A, Boiardi A, Broggi G, Marras C.2007. Expression of cannabinoid receptors and neurotrophins in human gliomas. NeurologicalSciences,28:304~310
Calissano M and Latchman D S.2010. Cell-specific regulation of the pro-survival Brn-3b transcriptionfactor by microRNAs. Mol Cell Neurosci,45(4):317~323
Cantarella G, Lempereur L, Presta M, Ribatti D, Lombardo G, Lazarovici P, Zappala G, Pafumi C,Bernardini R.2002. Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro andin vivo. FASEB J,16:1307~1309
Caporali A, Pani E, Horrevoets A J, Kraenkel N, Oikawa A, Sala-Newby G B, Meloni M, Cristofaro B,Graiani G, Leroyer A S, Boulanger C M, Spinetti G, Yoon S O, Madeddu P, Emanueli C.2008.Neurotrophin p75receptor (p75NTR) promotes endothelial cell apoptosis and inhibits angiogenesis.Implications for diabetesinduced impaired neovascularization in ischemic limb muscles. Circ Res,103:15~26
Caporali A, Sala-Newby G B, Meloni M, Graiani G, Pani E, Cristofaro B, Newby A C, Madeddu P,Emanueli C.2008. Identification of the prosurvival activity of nerve growth factor on cardiacmyocytes. Cell Death Differ,15:299~311
Capsoni S, Giannotta S, Cattanco A.2002. Nerve growth factor and galantatl1ine anleliorate earlv signs ofneurodegeneration in anti Nerve growth factor mice. Proc Natl Acad Sci USA,99(19):12432~12437
Carmeliet P.2005. Angiogenesis in life，disease and medicine. Nature,438:932~936
Carter B D, Kaltschmidt C, Kaltschmidt B, Offenhauser N, Bohm-Matthaei R, Baeuerle P A, Barde Y A.1996. Selective activation of NF-kappa B by nerve growth factor through the neurotrophin receptorp75. Science,272:542~545
Casaccia-Bonnefil P, Kong H，Chao M V.1998. Neurotrophins: the biological paradox of survival factorseliciting apoptosis. Cell Death Differ,5:357~364
Cassiman D, Denff C, Desmet V J, Roskams T.2001. Human and rat hepatic stellate cells expressneurotrophins and neurotrophin receptors. Hepatology,33(1):148~158
Chang K S.1991. Down-regulation of c-Ki-ras2gene expression associated with morphologic
differentiation in human embryonal carcinoma cells treated with berberine. J formos Med Assoc,90:10~14
Chang K S, Gao C, Wang L C.1990. Berberine-induced morphologic differentiation and down-regulationof c-ki-ras2protooncogene expression in human teratocarcinoma cells. Cancer Letter,55:103~108
Chao H Y, Ye L, Karen D, Nylander, Nina F S.2002. Trk A as a Life and Death Receptor: Receptor Doseas a Mediator of Function. Cancer Research,62:4867~4875
Chao M W.2003. Neurotrophins and their receptors: a convergence point for many signalling pathways.Nat. Rev. Neurosci,4:299~309
Chen R H，Sarnecki C and Bienis J.1992. Nuclear localization and regulation of erk-and rsk-encodedprotein kinases. Mol Cell Biol,12:915~927
Chen X Q, Fawcell J R, Rahman Y E.1998. Dellvry of nerve growth factor to the brain via the olfactorypathway. J Alzheimers Dis,1(1):35~44
Cheung W M，Hui W S，Chu P W, Chiu S W，Nancy Y.2000．Ganoderma extract activates MAP kinasesand induces the neuronal differentiation of rat pheochromocytoma PC12cels. FEBS Lett,86:291~296
Chiaretti X, Li R, Gentleman A, Vitale M, Vignetti F, Mandelli J, Ritz and Foa R.2004. Gene expressionprofile of adult t-ell acute lymphocytic leukemia identifies distinct subsets of patients with differentresponse to therapy and survival. Blood,103(7):2771~778
Christian G Z, Flavie S, Peter L, Stefan R B, Monika E B, Alexander W K.2008. DehydroepiandrosteroneInduces a Neuroendocrine Phenotype in Nerve Growth Factor-stimulated ChromaffinPheochromocytoma PC12Cells. Endocrinology,149(1):320~328
Combaret V，Gross N，Lasset C，Frappaz D，Beretta-Brognara C，Philip T，Beck D，Favrot MC.1997.Clinical relevance of CD44cell surface expression and MYCN gene amplification in neuroblastoma.Eur J Cancer,33(12):2101~2105
Connell S R, Trieber C A, Stelzl U, Einfeldt E, Taylor D E and Nierhaus K H2002. The tetracyclineresistance protein, Tet (O), perturbs the conformation of the ribosomal decoding center. Mol Microbiol,45:1463~1472
Corbit K C, Foster D A, Rosner M R.1999. Protein kinase Cdelta mediates neurogenic but not mitogenicactivation of mitogen-activated protein kinase in neuronal cells. Mol Cell Biol,19(6):4209~4218
Coulson E J, Reid K, Baca M, Shipham K A, Hulett S M, Kilpatrick T J, Bartlett P F.2000. Chopper，anew death domain of the p75neurotrophin receptor that mediates rapid neuronal cell death. J BiolChem,275:30537~30545
Coulson T, Catchpole E A, Albon S D, Morgan B J T, Pemberton J M, Clutton-Brock T H, Crawley M J,and Grenfell B T.2001. Age, sex, density, winter weather, and population crashes in Soay Sheep.Science,292:1528~1531
Countaway J L，Nairn A C and Davis R J.1992. Mechanism of desensitization of the epidermal growthfactor receptor protein-tyrosine kinase. J Biol Chem,267:1129~1140
Crowley C, Spencer S D, Nishimura M C, Chen K S, Pitts-Meek S, Armanini M P, Ling L H, McMahon SB, Shelton D L, Levinson A D.1994. Mice lacking nerve growth factor display perinatal loss ofsensory and sympathetic neurons yet develop basal forebrain cholinergic neurons. Cell,76:1001~1011
Daub H, Weiss F U, Wallasch C, Ullrich A.1996. Role of transactivation of the EGF receptor in signallingby G-protein-coupled receptors. Nature,379:557~560
Davies J A, Vodak P, Wilmore J H, Vodak J, Kurtz P.1976. Anaerobic threshold and maximal aerobicpower for three modes of excerise. J Appl Physiol,41:544~550
Davidson B, Reich R, Lazarovici P, Nesland J M, Skrede M, Risberg B, Trope C G, Florenes V A.2003.Expression and activation of the nerve growth factor receptor Trk A in serous ovarian carcinoma. ClinCancer Res,9:2248~2259
Dechant G and Barde Y A.2002. The neurotrophin receptor p75(NTR): novel functions and implicationsfor diseases of the nervous system. Nat Neurosci,5:1131~1136
Dechant G and Barde Y A.1997. Signalling through the neurotrophin receptor p75NTR. Curr OpinNeurobiol,7:413~418
Descamps O S，Gilbeau J P，Leysen X，Van Leuven F，Heller F R.2001b. Impact of genetic defects onatherosclerosis in patients suspected of familial hypercholesterolaemia. Eur J Clin Invest,31(11):958~965
Descamps S，Le Bourhis X，Delehedde M，Boilly B and Hondermarck H.1998. Nerve growth factor ismitogenic for cancerous but not normal human breast epithelial cells. J Biol Chem,273(27):16659~16662
Descamps S，Toillon R A，Adriaenssens E，Pawlowski V，Cool S M，Nurcombe V，Le Bourhis X，Boilly B，Peyrat J P，Hondermarck H.2001a. Nerve growth factor stimulates proliferation and survivalof human breast cancer cells through two distinct signaling pathways. J Biol Chem,276:17864~17870
Dikic I，Schlessinger J and Lax I.1994. PC12cells overexpressing the insulin receptor undergoinsulin-pendent neuronal differentiation. Curr Biol,4:702~708
Dolle J P, Rezvan A, Allen F D, Lazarovici P, Lelkes P I.2005. Nerve growth factor-induced migration ofendothelial cells. J Pharmacol Exp Ther,315:1220~1227
Dolle L，Yazidi-Belkoura I E，Adriaenssens E，Nurcombe V and Hondermarck H.2003. Nerve growthfactor overexpression and autocrine loop in breast cancer cells. Oncogene,22:5592~5601
Dong M, Chen S P, Kita K, Ichimura Y, Guo W Z, Lu S, Sugaya S, Hiwasa T, Takiguchi M, Mori N,Kashima A, Morimura K, Hirota M&Suzuki N.2009. Anti-proliferative and apoptosis-inducibleactivity of Sarcodonin G from Sarcodon scabrosus in HeLa cells. International Journal of Oncology,34:201~207
Donovan M J, Hahn R, Tessarollo L, Hempstead B L.1996. Identification of an essential nonneuronalfunction of neurotrophin-3in mammalian cardiac development. Nat Genet,14:210~213
Donovan M J, Lin M I, Wiegn P, Ringstedt T, Kraemer R, Hahn R, Wang S, Ibanez C F, Rafii S,Hempstead B L.2000. Brain derived neurotrophic factor is an endothelial cell survival factor requiredfor intramyocardial vessel stabilization. Development,127:4531~4540
Dragunow M, Mac Gibbon G A, Lawlor P, Butterworth N, Connor B, Henderson C, Walton M, WoodgateA, Hughes P, and Faull R L M.1998. Apoptosis，neurotrophic factors and neurodegeneration.Neurosciences,8:223~265
Duchemin B，Berthelot B，Dedieu G，Leroy M and Maisongrande P.2002. Normalisation of directionaleffects in10-day global syntheses derived from VEGETATION/SPOT: II. Validation of anoperational method on actual data sets. Remote Sensing of Environment,81:101~113
Emanueli C, Salis M B, Pinna A, Graiani G, Manni L, Madeddu P.2002. Nerve growth factor promotesangiogenesis and arteriogenesis in ischemic hindlimbs. Circulation,106:2257~2262
Emmett C J, Stewart G R, Johnson R M, Aswani S P, Chan R L, Jakeman L B.1996. Distribution ofRadioiodinated Recombinant Human Nerve Growth Factor in Prinate Brain FollowingIntracerebroventricular Infusion. Experimental Neurology,140(2):151~160
Eric M M, SeungY Y, Steven W F, Tae-Kyung K, Yingxi L, Robert S Hill, Nahit M M, Soher B,GenerosoG, Asif H, Samira A S, Janice W, Robert M J, Rachel G, Danielle G, Julia A E, Kira A A, Adria B,Jennifer N P, Brenda B, Hui Y, Kyriacos M, Russell J F, Michael E G, Christopher A W. IdentifyingAutism Loci and Genes by Tracing Recent Shared Ancestry. Science,321:218~223
Fanburg-Smith J C and Miettinen M.2001. Low-affinity nerve growth factor receptor (p75) indermatofibrosarcoma protuberans and other nonneural tumors: a study of1,150tumors and fetal andadult normal tissues. Hum Pathol,32:976~983
Feng J T, Hu C P.2005. Dysfunction ofreleasing adrenalinein asthmaby nerve growth factor. MedHypotheses,65(6):1043~1046
Fitzgerald M, Wall P D, Goedert M, Emson P C.1985. Nerve growth factor counteracts theneurophysiological and neurochemicaleffects of chronic sciatic nerve section. Brain Res,332:131~141
Frances A B and David A F.2000. Differential feedback regulation of the MAPK cascade underlies thequantitative differences in EGF and NGF signalling in PC12cells. FEBS Letters,482(3):169~174
Freund A, Jolivel V, Durand S, Kersual N, Chalbos D, Chavey C, Vignon F, and Lazennec G.2004.Mechanisms underlying differential expression of interleukin-8in breast cancer cells. Oncogene,23:6105~6114
Foehr E D，Lin A，O'Mahony R，Geleziunas R A，Bradshaw and Greene W C.2000. NF-kappa B signalingpromotes both cell survival and neurite process formation in nerve growth factor-stimulated PC12cells. J Neurosci,20:7556~7563
Folkman J.1995. Angiogenesis in cancer，vascular，rheumatoid and other disease. Nature Med,1:27~31
Fukuda M.1995. Carbohydrate-dependent cell adhesion. Bioorganic&Medicinal Chemistry,3(3):207~215
Furukawa S, Furukawa Y, Satoyoshi E, Hayashi K.1986. Synthesis and secretion of nerve growth factor bymouse astroglial cells in culture. Biochemical and Biophysical Research Communications,136(1):57~63
Gabriele U, Sara M, Sonia C, Antonino C, and Flaminia P. The function neutralizing Anti-TrkA antibodyMNAC13reduces inflammatory and neuropathic pain. PNAS,104(8):2985~2990
Gao J M.2006. New biologically active metabolites from chinese higher fungi. Curr Org Chem,10(8):849~871
Gao L, Xiang L, Luo Y, Wang G, Li J, Qi J.2010. Gentisides C-K: nine new neuritogenic compounds fromthe traditional Chinese medicine Gentiana rigescens Franch. Bioorg Med Chem,18(19):6995~7000
Gentry J J，Casaccia-Bonnefil P，Carter B D.2000. Nerve growth factor activation of nuclear factor kappaBthrough its p75receptor is an anti-apoptotic signal in RN22schwannoma cells. J Biol Chem,275:7558~7565
Gille H and Downward J.1999. Multiple ras effector pathways contribute to G (1) cell cycle progression. JBiol Chem,274:22033~22040
Goedert M，Spillantini M G，Jakes R，Rutherford D and Crowther R A.1989. Multiple isoforms of humanmicrotubule associated protein tau:sequences and localization in neurofibrillary tangles of Alzheimer’sdisease. Neuron,3:519~526
Goss G G，Perry S F，Fryer J N and Laurent P.1998. Gill morphology and acid-base regulation infreshwater fishes. Comp Biochem Physiol,119:107~115
G tz R，K ster R，Winkler C，Raulf F，Lottspeich F，Schartl M，Thoenen H.1994. Neurotrophin-6isa new member of the nerve growth factor family. Nature,372:266~269
Graiani G, Emanueli C, Desortes E, Van Linthout S, Pinna A, Figueroa C D, Manni L, Madeddu P.2004.Nerve growth factor promotes reparative angiogenesis and inhibits endothelial apoptosis in cutaneouswounds of Type1diabetic mice. Diabetologia,47:1047~1054
Granholm A C, Albeck D, Backman C, Curtis M, Ebendal T, Friden P, Henry M, Hoffer B, Kordower J,Rose G M.1998. A non-invasive system for delivering neural growth factors across the blood-brainbarrier: a review. Rev Neurosci,9(1):31~55
Greene L A and Tischler A S.1976. Establishment of a noradrenergic clonal line of rat adrenalpheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci,3(7):2424~2428
Grewal S S, York R D, Stork P J.1999. Extracellular-signal-regulated kinase signalling in neurons. CurrOpin Neurobiol,9:544~553
Grundman M, Jack C R J, Petersen R C, Kim H T, Taylor C, Datvian M, Weiner M F, DeCarli C, DeKoskyS T, van Dyck C H, Darvesh S, Yaffe K, Kaye J, Ferris S H, Thomas R G, Thal L J.2003.Hippocampal volume is associated with memory but not nonmemory cognitive performance inpatients with mild cognitive impairment. J Mol Neurosci,20:241~248
Gu Le, Shen Y, Xu S, Shu Y, Jiang T, Lin Z.2002. Crystallization and preliminary X-ray diffractionstudies of cobra venom beta-nerve growth factor. Biochem Biophys Res Commun,297(4):1008~1010
Haimovitz-Friedman A，Kolesnick R N，Fuks Z.1997. Ceramide signaling in apoptosis. Br Med Bull,53(3):539~553
Hallb k F，Ibanez C F，Persson H.1991. Evolutionary studies of the nerve growth factor family reveal anovel member abundantly expressed in Xenopus ovary. Neuron,6:845~858
Hanahan D and Folkman J.1996. Patterns and emerging mechanisms of the angiogenic switeh duringtumorigenesis. Cell,86:353~364
Hashimoto R, Takei N, Shimazu K, Christ L, Lu B, Chuang D M.2002. Lithium induces brain-derivedneurothophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotectionagainst glutamate excitotoxicity. Neuropharmacology,43:1l73~1179
Hashimoto S and Hagino A.1989. Staurosporine-induced neurite outgrowth in PC12h cells. Exp Cell Res,184(2):351~359
Hassankhani A, Steinhelper M E, Soonpaa M H, Katz E B, Taylor D A, Andrade-Rozental A, Factor S M,Steinberg J J, Field L J, Federoff H J.1995. Overexpression of NGF within the heart of transgenicmice causes hyperinnervation，cardiac enlargement and hyperplasia of ectopic cells. Dev Biol,169:309~321
Hawksworth D L.2001. The magnitude of fungal diversity: the1.5million species estimate revisited.Mycol Res,105(12):1422~1432
Heasley L E，Johnson G L.1992. The13PDGF receptor induces neuronal differentiation of PC12cells.Mol Biol Cell,3:545~553
Hefti F, Hartikka J, Knusel B.1989. Function of neurotrophic factors in the adult and their possible use inthe treatment of neurodegenerative disease. Neurobiol Aging,10:515~533
Hefti F F, Rosenthal A, Walicke P A, Wyatt S, Vergara G, Shelton D L, Davies A M.2006. Novel class ofpain drugs based on antagonism of NGF. Trends Pharmacol Sci,27:85~91
Hempstead B L, Martin-Zanca D, Kaplan D R, Parada L F, Chao M V.1991. High-affinity NGF bindingrequires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature,350:678~683
Hernandez C M，Terry A V Jr.2005. Repeated nicotine exposure in rats: effects on memory function,cholinergic markers and nerve growth factor. Netroscience,130:997~l0l2
Herzberg U，Eliav E，Dorsey J M，Gracely R H，Kopin I J.1997. NGF involvement in pain induced bychronic constriction injury of the rat sciatic nerve. NeuroReport,8:1613~1618
Higuchi M, Onishi K, Masuyama N, Gotoh Y.2003. The phosphatidylinositol-3kinase (PI3K)-Aktpathway suppresses neurite branch formation in NGF-treated PC12cells. Genes to Cells,8:657~669
Hines J，Groll M，Fahnestock M and Craig M.2008. Proteasome Inhibition by Fellutamide B InducesNerve Growth Factor Synthesis. Chemistry&Biology,15:501~512
Hirota M, Morimura K, Shibata H.2002. Anti-inflammatory compounds from the bitter mushroom,Sarcodon scabrosus. Biosci Biotech Bioch,66(1):179~184
Hohn A, Leibrock J, Bailey K, Barde Y A.1990. Identification and characterization of a novel member ofthe nerve growth factor/brain-derived neurotrophic factor family. Nature,344:339~341
Huang E J and Reichardt L F.2001. Neurotrophins: roles in neuronal development and function. Annu RevNeurosci,24:677~736
Huang E and Reichardt L.2003. Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem,72:609~642
Hur J Y, Lee P，Kim H，Kang I, Lee K R, Kim S Y.2004．(-)-3，5-Dicaffeoyl-muco-quinic acid isolatedfrom Aster scaber contributes to the differemiation of PC12cells: the tyrosine kinase cascadesignaling. Biochem Biophys Res Commun,313:948~953
Ibanez C F.1994. Structure-function relatiomships in the neurotrophin family. J Neurobiol,25(11):1349~1361
Ieda M, Fukuda K, Hisaka Y, Kimura K, Kawaguchi H, Fujita J, Shimoda K, Takeshita E, Okano H,Emanueli C, Salis M B, Pinna A, Graiani G, Manni L, Madeddu P.2002. Nerve growth factorpromotes angiogenesis and arteriogenesis in ischemic hindlimbs. Circulation,106:2257~2262
Iizuka N, Miyamoto K, Okita K, Tangoku A, Hayashi H, Yosino S, Abe T, Morioka T, Hazama S, Oka M.2000. Inhibltory effect of Coptidis Rhizoma and berberine on the proliferation of human esophagealcancer cell lines. Cancer Lett,148:19~25
Inoue K, Kulsum U, Chowdhury S A, Fujisawa S, Ishihara M, Yokoe I, Sakagami H.2005. Tumor-specificcytotoxicity and apoptosis-inducing activity of berberines. Anticancer Res,25:4053~4059
Itzhak K，Jashovam S，Goshen G，Sela J.2003. Characterization of nerve growth factors (NGFs) fromsnake venoms by use of a novel，quantitative bioassay utilizing pheochromocytoma (PC12) cellsoverexpressing human trkA receptors. Toxicon,42:481~490
Iwasa K, kamigauchi M, Suglura M, Nanba H.1997. Antimicrobal activity of some13-alkayl-substitutedprotoberberinium salts. Planta Med,63:196~198
Izabela S, Ilker K S, Shimon L, Meghan C. B, Erin M W, George P T, Mahmut S, Philip L and Cezary M.Integrin α9β1is a receptor for nerve growth factor and other neurotrophins. Journal of Cell Science,121:504~513
Jackson R M，Parish G and Ho Y S.1996. Effects of hypoxia on expression of superoxide dismutases incultured ATII cells and lung fibroblasts. Am. J. Physiol. Lung Cell Mol. Physiol,271:955~962
Jeanneteau F，Garabedian M J and Chao M V.2008. Activation of Trk neurotrophin receptors byglucocorticoids provides a neuroprotective effect. PNAS,105:4862~4867
Julius D and Basbaum A I.2001. Molecular mechanisms of nociception. Nature,413:203~210
Jung S S, Eung Il K, Masaaki K, and Myung K L.2000. Inhibition of Dopamine Biosynthesis byProtoberberine Alkaloids in PC12Cells. Neurochemical Research,25(3):363~368
Jung S S, Yu M K, Seong S H, Ho S K, Yoo J Y, Don K L, Bang Y H, Jai S R and Myung K L.2005.Induction of neurite outgrowth by (-)-(7R,8S)-dihydrodehydrodiconiferyl alcohol from PC12cells.Archives of Pharmacal Research,28:1337~1340
Kamata H, Tanaka C, Yagisawa H, Matsuda S, Gotoh Y, Nishida E, Hirata H.1996. Suppression of nervegrowth factor-induced neuronal differentiation of PC12cells. N-acetylcysteine uncouples the signaltransduction from ras to the mitogen-activated protein kinase cascade. J Biol Chem,271:33018~33025
Kamei Y, Tsang C K.2003. Sargaquinoic acid promotes neurite outgrowth via protein kinase A and MAPkinases-mediated signaling pathways in PC12D cells. J Dev Neurosci,21(5):255~262
Kao S, Jaiswal R K, Kolch W, Landreth G E.2001. Identification of the mechanisms regulating thedifferential activation of the mapk cascade by epidermal growth factor and nerve growth factor inPC12cells. J Biol Chem,276:18169~18177
Kaplan D R and Miller F D.2000. Neurotrophin signal transduction in the nervous system. Curr. Opin.Neurobiol,10:381~391
Kawagishi H, Shimada A, Hosokawa S, Mori H, Sakamoto H, Ishiguro Y, Sakemi S, Bordner J, Kojima N,Furukawa S.1996a. Erinacines E，F and G，stimulators of nerve growth factor (NGF)-synthesis, fromthe mycelia of Hericium erinaceum. Tetrahedron Lett,37(41):7399~7402
Kawagishi H, Simada A, Shizuki K, Mori H, Okamoto K, Sakamoto H, Furukawa S.1996b. Erinacine D, astimulator of NGF-synthesis, from the mycelia of Hericium erinaceum. Heterocycl Commun,2(1):51~54
Kawagishi H, Shimada A, Shirai R, Okamoto K, Ojima F, Sakamoto H, Ishiguro Y, Furukawa S.1994.Erinacines A, B and C, strong stimulators of nerve growth factor (NGF)-synthesis, from the myceliaof Hericium erinaceum. Tetrahedron Lett,35(10):1569~1572
Kawaguchi-Manabe H, Ieda M, Kimura K, Manabe T, Miyatake S, Kanazawa H, Kawakami T, Ogawa S,Suematsu M, Fukuda K.2007. A novel cardiac hypertrophic factor, neurotrophin-3, is paradoxicallydownregulated in cardiac hypertrophy. Life Sci,81:385~392
Kenmoku H, Sassa T, Kato N.2000. Isolation of erinacine P, a new parental metabolite ofcyathane-xylosides, from Hericium erinaceum and its biomimetic conversion into erinacines A and B.Tetrahedron Lett,41(22):4389~4393
Kenmoku H, Shimai T, Toyomasu T, Kato N, Sassa T.2002. Erinacine Q, a new erinacine from Hericiumerinaceum, and its biosynthetic route to erinacine C in the basidiomycete. Biosci Biotechnol Biochem,66(3):571~575
Kenzo C, Matsumi Y, Masafumi K, Rie K, Masao K.2011. New physiological function of secoiridoids:neuritogenic activity in PC12h cells. J Nat Med,65:186~190
Khan K M, Falcone D J, Kraemer R.2002. Nerve growth factor activation of Erk-1and Erk-2inducesmatrix metalloproteinase-9expression in vascular smooth muscle cells. J Biol Chem,277:2353~2359
Kim H, Li Q, Hempstead B L, Madri J A.2004. Paracrine and autocrine functions of brain-derivedneurotrophic factor (BDNF) and nerve growth factor (NGF) in brain-derived endothelial cells. J BiolChem,279:33538~33546
Kim S, Shin D S, Lee T, Oh K B.2004. Periconicins, two new fusicoccane diterpenes produced by anendophytic fungus Periconia sp. with antibacterial activity. J Nat Prod,67(3):448~450
Kirk P M, Cannon P F, David J C, Stalpers J A.2001. Ainsworth&Bisby's dictionary of the fungi. In9thed, Wallingford, UK: CAB International
Kishibe K, Yamada Y, Ogawa K.2002. Production of nerve growth factor by mouse hepatocellularcarcinoma cells and expression of TrkA in tumor-associated arteries in mice. Gastroenterology,122:1978~1986
Kita T, Takaya Y, Oshima T Y.1998. Scabronines B，C，D，E and F，novel diterpenoids showingstimulating activity of nerve growth factor-synthesis, from the mushroom Sarcodon scabrosus.Tetrahedron,54(39):11877~11886
Kobayashi T, Kishigami S, Sone M, Inokuchi H, Mogi T and Ito K.1997. Respiratory chain is required tomaintain oxidized states of the DsbA-DsbB disulfide bond formation system in aerobically growingEscherichia coli cells. Proc Natl Acad Sci USA,94:11857~11862
Kogner P，Bj rk O and Theodorsson E.1993. Neuropeptide Y in neuroblastoma: increased concentration inmetastasis, release during surgery, and characterization of plasma and tumor extracts. Med PediatOncol,21:317~322
Kohn J, Aloyz R S, Toma J G, Haak-Frendscho M, Miller F D.1999. Functionally antagonistic interactionsbetween the TrkA and p75neurotrophin receptors regulate sympathctic neuron growth and targetinncrvation. J Neurosci,19:5393~5408
Koizumi S, Contreras M L, Matsuda Y, Hama T, Lazarovici P and Guroff G.1988. K-252a: A SpecificInhibitor of the Action of Nerve Growth Factor on PC12Cells. Neuroscience,8(2):715~721
Kolb B, C té S, Ribeiro-da-Silva A, Cuello A C.1997. Nerve growth factor treatment prevents dendriticatrophy and promotes recovery of function after cortical injury. Neuroscience,76(4):1139~1151
Koltzenburg M, Bennett D L H, Shelton D L, McMahon S B.1999. Neutralization of endogenous NGFprevents the sensitization of nociceptors supplying inflamed skin. Eur J Neurosci,11:1698~704
Kuroyanaci M, Ikeda R, Gao H Y, Muto N, Otaki K, Sano T, Kawahara N and Nakane T.2008.ChemInform Abstract: Neurite Outgrowth-Promoting Active Constituents of the Japanese Cypress(Chamaecyparis obtusa). Chem Pharm Bull,56:60~63
Küpeli E, Kosar M, Yesilada E, Hüsnü K, Baser C.2002. A comparative study on the anti-inflammatory,antinociceptive and antipyretic effects of isoquinoline alkaloids from the roots of Turkish Berberisspecies. Life Sci,72:645~657
Kuroyanagi M, Ikeda R, Gao H Y, Muto N, Otaki K, Sano T, Kawahara N, Nakane T.2008. Neuriteoutgrowth-promoting active constituents of the Japanese cypress (Chamaecyparis obtusa). ChemPharm Bull,56(1):60~63
Kuruvilla R, Ye H, Ginty D D.2000. Spatially and functionally distinct roles of the PI3-K effector pathwayduring NGF signaling in sympathetic neurons. Neuron,27(3):499~512
Lapthorn A J, Harris D C, Littlejohn A, Lustbader J W, Canfield R E, Machin K J, Morgan F J.1994.Cystal structure of human chorionic gonadotropin. Nature,369:455~461
Lavoie J G，O'Neil J，Sanderson L，Elias B，Mignone J，Bartlett J.2005. The National Evaluation of thehealth transfer policy, final report Winnipeg: Manitoba First Nations Centre for Aboriginal HealthResearch.
Lazarovici P, Gazit A, Staniszewska I, Marcinkiewicz C, Lelkes P I.2006. Nerve growth factor (NGF)promotes angiogenesis in the quail chorioallantoic membrane. Endothelium,13:51~59
Lee M K and Zhang Y H.1996. Inhibition of tyrosine hydro-xylase by berberine. Med Sci Res,24:561~562
Lee F S，Rajagopal R，Kim A H，Chang P C and Chao M V.2002. Activation of Trk neurotrophin receptorsignaling by pituitary adenylate cyclase-activating polypeptides. J Biol Chem,277:9096~9102
Lee F S and Chao M V.2001. Activation of Trk neurotrophin receptors in the absence of neurotrophins.Proc Natl Acad Sci USA,98:3555~3560
Lee M K，Zhang Y H and Kim H S.1996. Inhibition of tyrosine hydroxylase by palmatine. Arch PharmRes,19:258~260
Lee R，Kermani P, Teng K K and Hempstead B L.2001. Regulation of cell survival by secretedproneurotrophins. Science,294:1945~1948
Leon A, Buriani A, Dal Toso R, Fabris M, Romanello S, Aloe L and Levi-Montalcini R.1994. Mast cellssynthesize, store, and release nerve growth factor. Proc Natl Acad Sci USA,91:3739~3743
Letasiova S, Jantova S, Miko M, Ovadekova R, Horvathova M.2006. Effect of berberine on Proliferation,biosynthesis of macromolecules, cell cycle and induction of intercalation with DNA, dsDNA demageand apoptosis in Ehrlich ascites carcinoa cells. J Phanu Pharmcol,58:263~270
Levi-Montalcini R and Hamburger V.1953. A diffusible agent of mousesarcoma producing hyperplasia ofsympathetic ganglia and hyperneurotization of viscera in the chick embryo. J Exp Zool,123:233~278
Levi-Montalcini R.1987. The nerve growth factor35years later. Science,237:1154~1162
Levi-Montalcini R，Skaper S D，Dal Toso R，Petrelli L and Leon A.1996. Nerve growth factor: fromneurotrophin to neurokine. Trends Neurosci,19:514~520
Lewin G R and Barde Y A.1996. Physiology of the neurotrophins. Ann Rev Neurosci,19:289~317
Lewin G R and Mendell L M.1993. Nerve growth factor and nociception.Trends Neurosci,16:353~359
Lichtman J W，Magrassi L and Purves D.1987. Developmental neurobiology. Trophic factor theorymatures. Nature,326(6111):336
Li L, Xian C J, Zhong J H, Zhou X F.2003. Upregulation of brain-derived neurotrophic factor in thesensory pathway by selective motor nerve injury in the adult rats. Neurotoxicity Research,9:269~283
Li P, Matsunaga K, Yamakuni T, Ohizumi Y.2000. Potentiation of nerve growth factor-action bypicrosides I and II，natural iridoids，in PC12D cells. Eur J Pharmacol,406:203~208
Li P, Yamakuni T, Mutsunaga K, Ohizumi Y.2003. Nardosinone enhances nerve growth factor-inducedneurite outgrowth in a mitogen-activated protein kinase and protein kinase C-dependent manner inPC12D cells. J Pharmacol Sci,93:122~125
Li T K, Bathory E, Lovoie E J, Srinivasan A R, Olson W K, Sauers R R, Liu L F, Pilch D S.2000. Humantopolsomerase l poisoning by Protoberberine: potention roles for both drug-DNA and drug-enzymeinteration. Biochemistry,39(24):7107~7116
Li Y S, Matsunaga K, Kato R, Ohizumi Y.2001. Potentiation of nerve growth factor-induced elongation ofneurites by gelsemiol and9-hydroxysemperoside aglucone in PC12D cells. J Pharm Phanmwol,53:915~919
Lin M I, Das I, Schwartz G M, Tsoulfas P, Mikawa T, Hempstead B L.2000. Trk C receptor signalingregulates cardiac myocyte proliferation during early heart development in vivo. Dev Biol,226:180~191
Liu J H, Jiang B, Bao Y M, An L J.2003. Effect of Cuscuta chinensis glycoside on the neuronaldiferentiation of rat pheochromocytoma PC12cells. Neuroscience,21:277~281
Liu J K.2006. Natural Terphenyls: Developments since1877. Chem rev,106(6):2209~2223
Liu Yu-li.2004. Dial-a-Porn Services in Taiwan: A Legal Perspective. In P.Lee, L.Leung,&C.So.(Eds).Impact and Issues in New Media: Toward Intelligent Societies. London: Hampton Press
Luttrell L M, Daaka Y, Lefkowitz R J.1999. Regulation of tyrosine kinase cascades by G-protein-coupledreceptors. Curr Opin Cell Biol,11:177~183
MacDonald J I，Gryz E A，Kubu C J，Verdi J M and Meakin S O.2000. Direct binding of the signalingadapteprotein Grb2to the activation loop tyrosines on the nerve growth factor receptor tyrosine kinase,Trk A. J Biol Chem,275:18225~18233
Maisonpierre P C, Belluscio L, Friedman B, Alderson R F, Wiegand S J, Furth M E, Lindsay R M,Yancopoulos G D.1990. NT-3, BDNF, and NGF in the developing rat nervous system: parallel aswell as reciprocal patterns of expression. Neuron,5:501~509
Mallei A，Rabin S J，Mocchetti I.2004. Autocrine regulation of nerve growth factor expression by Trkreceptors. J Neurochem,90:1085~l093
Mamidipudi V, Li X, Wooten M W.2002. Identification of interleukin1receptor-associated kinase as aconserved component in the p75-neurotrophin receptor activation of nuclear factor-kappa B. J BiolChem,277:28010~28018
Marcotullio M C, Pagiotti R, Campagna V, Maltese F, Fardella G, Altinier G, Tubaro A.2006b.Glaucopine C, a new diterpene from the fruiting bodies of Sarcodon glaucopus. Nat Prod Res,20(10):917~921
Marcotullio M C, Pagiott R, Maltese F, Obara Y, Hoshino T, Nakahata N, Curini M.2006a. Neuriteoutgrowth activity of cyathane diterpenes from Sarcodon cyrneus, cyrneines A and B. Planta Med,72(9):819~823
Marcotullio M C, Pagiotti R, Maltese F, Oball-Mond Mwankie G N, Hoshino T, Obara Y, Nakahata N.2007. Cyathane diterpenes from Sarcodon cyrneus and evaluation of their activities of neuritegenesisand nerve growth factor production. Bioorg Med Chem,15(8):2878~2882
Marshall C J.1995. Specificity of receptor tyrosine kinase signaling: transient versus sustainedextracellular signal-regulated kinase activation. Cell,80:179~185
Mayumi-Matsuda K，Kojima S，Suzuki H and Sakata T.1999. Identification of a novel kinase~like geneinduced during neuronal cell death. Biochem Biophys Res Commun,258:260~264
McDonald N Q, Lapatto R, Murray-rust J, Gunning J, Wlodawer A, Blundell T L.1991. New protein foldrevealed by a2-3-A resolution crystal structure. Nature,354:411~415
McGregor L M, McCune B K, Graff J R, McDowell P R, Romans K E, Yancopoulos G D, Ball D W,Baylin S B, Nelkin B D.1999. Roles of trk family neurotrophin receptors in medullary thyroidcarcinoma development and progression. Proc Natl Acad Sci USA,96:4540~4545
McMahon S B, Bennett D L, Priestley J V, Shelton D L.1995. Biological effects of endogenous nervegrowth factor on adult sensory neurons revealed by a trkA-IgG fusion molecule. Nat Med,1:774~780
Meakin S O，MacDonald J I，Gryz E A，Kubu C J，Verdi J M.1999. The signaling adapter FRS-2competeswith Shc for binding to the nerve growth factor receptor TrkA. A model for discriminatingproliferation and differentiation. J Biol Chem,274:9861~9870
Middeke M, Hoffmann S, Hassan I, Wunderlich A, Hofbauer L C, Zielke A.2002. In vitro and in vivoangiogenesis in PC12pheochromocytoma cells is mediated by vascular endothelial growth factor. ExpClin Endocrinol Diabetes,110:386~392
Middlemiss P J, Glasky A J, Rathbone M P, Werstuik E, Hindley S, Gysbers J.1995. AIT-082, a uniquepurine derivative, enhances nerve growth factor mediated neurite outgrowth from PC12cells.Neuroscience Letters,191(2):131~134
Mizumaki Y, Kurimoto M, Hirashima Y, Nishijima M, Kamiyama H, Nagai S, Takaku A, Sugihara K,Shimizu M, Endo S.2002. Lipophilic fraction of Panax ginseng induces neuronal diferentiation ofPC12cells and promotes neuronal survival of rat conical neurons by protein kinase C dependentmanner. Brain Res,950:254~260
Mowla S J, Farhadi H F, Pareek S, Atwal J K, Morris S J, Seidah N G, Murphy R A.2001. Biosynthesisand post-translational processing of the precursor to brain-derived neurotrophic factor. J Biol Chem,276:12660~12666
Mufson E J, Kordower J H.1997. Nerve growth factor and its receptors in the primate forebrain: alterationin Alzheimer’s disease and potential use in experimental therapeutics. In: Mattson MP, editor.Neuroprotective signal transduction. Clifton, NJ: Humana Press.23~59.
Musiol IM and Feldman D.1997.1,25-Dihydroxyvitamin D-3induction of nerve growth factor in L929mouse fibroblasts: effect of vitamin D receptor regulation and potency of vitamin D-3analogs.Endocrinology,138:12~18
Nakagawara A.2001. Trk receptor tyrosine kinases: a bridge between cancer and neural development.Cancer Lett,169:107~114
Nassenstein C，Kutschker J，Tumes D and Braun A.2006．Neuro-immune interaction in allergic asthma:role of neurotrophins. Biochem Soc Trans,34(4):591~593
Naumann T, Casademunt E, Hollerbach E,2002. Complete deletion of the neurotrophin receptor p75NTRleads to long-lasting increases in the number of basal forebrain cholinergic neurons. Neurosci,22(7):2409~2418
Nemoto K, Fukamachi K, Nemoto F, Miyata S, Hamada M, Nakamura Y, Senba E, Ueyama T.1998. Geneexpression of neurotrophins and their receptors in cultured rat vascular smooth muscle cells. BiochemBiophys Res Commun,245:284~288
Nguyen T T, Scimeca J C, Filloux C, Peraldi P, Carpentier J L and van Obberghen E.1993. Co-regulationof the mitogen-activated protein kinase，extracellular signal-regulated kinase1and the90kDaribosomal$6kinase in PC12cells. J Biol Chem,268:9803~9810
Nico B, Mangieri D, Benagiano V, Crivellato E, Ribatti D.2008. Nerve growth factor as an angiogenicfactor. Microvasc Res,75:135~141
Nilsson A S, Fainziber M, Falck P, Ibanez C F.1998. Neurotrophin-7: a novel member of the neurotrophinfamily from the zebrafish. FEBS Lett,424:285~290
Nimnual A S, Yatsula B A, Bar-Sagi D.1998. Coupling of Ras and Rac guanosine triphosphatases throughthe Ras exchanger Sos. Science,279:560~63
Noekher W A, Reaz H.2006. Neurotrophins and asthma：novel insight into neuroimmune interaction. JAllergy Clin Immunol,117(1):67~7l
Nosaka Y, Arai A, Miyasaka N, Miura O.1999. CrkL mediates Rasdependent activation of the Raf/ERKpathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated witherythropoietin or interleukin-3. J Biol Chem,274:30154~30162
Nykjaer A, Lee R, Teng K K, Jansen P, Madsen P, Nielsen M S, Jacobsen C, Kliemannel M, Schwarz E,Willnow T E, Hempstead B L, Petersen C M.2004. Sortilin is essential for proNGF-induced neuronalcell death. Nature,427(6977):843~848
Obara Y，Aoki T，Kusano M and Ohizumi Y.2002. β-Eudesmol Induces Neurite Outgrowth in RatPheochromocytoma Cells Accompanied by an Activation of Mitogen-Activated Protein Kinase. JPET,301:803~811
Obara Y, Hoshino T, Marcotullio M C, Pagiotti R, Nakahata N.2007. A novel cyathane diterpene, cyrneineA, induces neurite outgrowth in a Rac1-dependent mechanism in PC12cells. Life Sci,80(18):1669~1677
Obara Y, Kobayashi H, Ohta T, Ohizumi Y, Nakahata N.2001. Scabronine G-methylester enhancessecretion of neurotrophic factors mediated by an activation of protein kinase C-zeta. Mol Pharmacol,59(5):1287~1297
Obara Y, Nakahata N, Kita T, Takaya Y, Kobayashi H, Hosoi S, Kiuchi F, Ohta T, Oshima Y, Ohizumi Y.1999. Stimulation of neurotrophic factor secretion from1321N1human astrocytoma cells by novelditerpenoids, scabronines A and G. Eur J Pharmacol,370(1):79~84
Obermeier A，Bradshaw R A，Seedorf K，Choidas A，Schles-singer J and UIIrich A.1994. Neuronaldifferentiation signals are controlled by nerve growth factor receptor/Trk binding sites for SHC andPLC~. EMBO,13:1585~1590
Ohta T, Kita T, Kobayashi N, Obara Y, Nakahata N, Ohizumi Y, Takaya Y, Oshima Y.1998. ScabronineA, a novel diterpenoid having potent inductive activity of the nerve growth factor synthesis, isolatedfrom the mushroom, Sarcodon scabrosus. Tetrahedron Lett,39(34):6229~623
Pages G，Lenorrnand P，LAllemain G，Chambard J C，Meloche S，Pouyssegur J.1993. Mitegen-activatedprotein kinases p42mapk and p44mapk are required for fibroblast proliferation. Proc Ned Acid SciUSA,90:8319~8323
Palko M E, Coppola V, Tessarollo L.1999. Evidence for a role of truncated trkC receptor isoforms inmouse development. J Neurosci,19:775~782
Park M J, Kwak H J, Lee H C, Yoo D H, Park I C, Kim M S, Lee S H, Rhee C H, Hong S I.2007. Nervegrowth factor induces endothelial cell invasion and cord formation by promoting matrixmetalloproteinase-2expression through the phosphatidylinositol3-kinase/Akt signaling pathway andAP-2transcription factor. J Biol Chem,282:30485~30496
Park S, Roming P W A, Hughes J P, Slane P O, Burrows D N, Garmire G P and Nousek J A.2002. TheStructure of the Oxygen-rich Supernova Remnant G292.0+1.8from Chandra X-Ray Images: ShockedEjecta and Circumstellar Medium. ApJ,564:39~44
Perez P，Coll P M，Hempstead B L，Martin-Zanca D, Chao M V.1995. NGF binding to the trk tyrosinekinase receptor requires the extracellular immunoglobulin-~like domains. Mol Cell Neurosci,6:97~105
Perry E K，Tomlinson B E，Blessed G，Bergmann K，Gibson P H and Perry R H.1978. Correlation ofcholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J，2:1457~1459
Peyssonnaux C，Provot S，Felder-Schmittbuhl M P，Calothy G and Eychène A.2000. Induction ofpostmitotic neuroretina cell proliferation by distinct Ras downstream signaling pathways. Mol CellBiol,20(19):7068~7079
Poo M-m.2001. Neurotrophins as synaptic modulators. Nat. Rev. Neurosci,2:24~31
Pradines A, Magazin M, Schiltz P, Le F, Caput D, Ferrara P.1995. Evidence for nerve growthfactor-potentiating activities of the non-peptidic compound SR57746A in PC12cells. J. Neurochem,64:1954~1964
Qi J H, Li X G，Feng L J，Zhang M P.2006.An x-ray photoelectron spectroscopy study of elements on thesurface of aerosol particles. Journal of Aerosol Science,37(2):218~227
Qian X and Ginty D D.2001. SH2-B and APS are multimeric adapters that augment TrkA signaling. MolCell Biol,21:1613~1620
Qui M S and Green S H.1992. PC12cell neuronal differentiation is associated with prolonged p21rasactivity and consequent prolonged ERK activity. Neuron,9:705~717
Rabizadeh S, Oh J, Zhong L T, Yang J, Bitler C M, Butcher L L, Bredesen D E.1993. Induction ofapoptosis by the low-affinity NGF receptor. Science,261:345~348
Rabizadeh S, Ye X, Wang J J and Bredesen D E.1999. Neurotrophin dependence mediated by p75NTR:contrast between rescue by BDNF and NGF. Cell Death Differ,6:1222~1227
Rahbek U L，Dissing S，Thomassen C，Hansen A J，Tritsaris K.2005. Nerve growth factor activates aortaendothelial cells causing PI3K/Akt-and ERK-dependent migration. Pflu gers Arch,450:355~361
Rajagopal R, Chen Z Y, Lee F S, Chao M V.2004. Transactivation of Trk neurotrophin receptors byG-protein-coupled receptor ligands occurs on intracellular membranes. J Neurosci,24:6650~6658
Raychaudhuri S K, Raychaudhuri S P, Weltman H, Farber E M.2001. Effect of nerve growth factor onendothelial cell biology: proliferation and adherence molecule expression on human dermalmicrovascular endothelial cells. Arch Dermatol Res,293:291~295
Raychaudhuri S P, Jiang W Y, Farber E M.1998. Psoriatic keratinocytes express high levels of nervegrowth factor. Acta Derm Venereol,78:84~86
Renné C，Minner S，Küppers R，Hansmann M L，Br uninger A.2008. Autocrine NGFbeta/TRKAsignallingis an important survival factor for Hodgkin lymphoma derived cell lines. Leuk Res,32(2):163~167
Reynolds B A and Weiss S.1992. Generation of neurons and astrocytes from isolated ce1ls of the adultmammalian central nervous system. Science,255(5052):1707~1710
Reynolds L P and Redmer D A.1998. Expression of the angiogenic factor，basic fibroblast growth factorand vascular endothelial growth factors. J Anim Sci,76:1671~1681
Ribatti D, Conconi M T, Nussdorfer G G.2007. Non-classical endogenous Novel regulators ofangiogenesis. Pharmacol Rev,59:185~205
Ribatti D, Presta M, Vacca A, Ria R, Giuliani R, Dell'Era P, Nico B, Roncali L, Dammacco F.1999.Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulatesneovascularization in vivo. Blood,93:2627~2636
Robinson C, Hynds P J, Robinson D, Mant A.1998. Multiple pathways for the targeting of thylakoidproteins in chloroplasts. Plant Molecular Biology,38:209~221
Ridley A J and Hall A.1992. The small GTP-binding protein rho regulates the assembly of focal adhesionsand actin stress fibers in response to growth factors. Cell,70:389~399
Rodrigues B and McNeill J H.1992. The diabetic heart: metabolic causes for the development of acardiomyopathy. Cardiovasc Res,26:913~922
Rodriguez-Tébar A, Dechant G and Barde Y A.1990. Binding of brain-derived neurotrophic factor to thenerve growth factor receptor. Neuron,4:487~492
Rodriguez-Tébar A, Dechant G, Gotz R, Barde Y A.1992. Binding of neurotrophin-3to its neuronalreceptors and interactions with nerve growth factor and brain-derived neurotrophic factor. EMBO J,11:917~922
Ruiz G, Ceballos D, Ba os JE.2004. Behavioral and histological effects of endoneurial administration ofnerve growth factor: possible implications in neuropathic pain. Brain Res,1011(1):1~6
Sahai E，Olson M F and Marshall C J.2001. Cross-talk between Ras and Rho signalling pathways intransformation favours proliferation and increased motility. EMBO J,20:755~766
Salehi A, Verhaagen J, Dijkhuizen P A, Swaab D F.1996. Co-localization of high-affinity neurotrophinreceptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer’s disease.Neuroscience,75:373~387
Salis M B, Graiani G, Desortes E, Caldwell R B, Madeddu P, Emanueli C.2004. Nerve growth factorsupplementation reverses the impairment, induced by Type1diabetes, of hindlimb post-ischaemicrecovery in mice. Diabetologia,47:1055~1063
Santos P M, Winterowd J G, Allen G G, Bothwell M A, Rubel E W.1991. Nerve growth factor: increasedangiogenesis without improved nerve regeneration. Otolaryngol Head Neck Surg,105:12~25
Scarisbrick I A，Jones E G，Isackson P J.1993. Coexpression of mRNAs for NGF，BDNF and NT-3in thecardiovascular system of the pre-and postnatal rat. J Neurosci,13:875~893
Schlessinger J.2000. Cell signaling by receptor tyrosine kinases. Cell,103:211~225
Schlessinger J and Barsagi D.1995. Activation of ras and other signaling pathways by tyrosine receptorkinases. Molecular Genetics of Cancer，vol.60. Cold Spring Harbor Laboratory Press: Cold SpringHarbor，NY.
Schmitt H R，Ulvestad J S，Antonucci R R J and Kinney A L.2001. ApJS,132:199
Schlunegger M P, Grutter M G.1993. Refined crystal structure of hTGFβ2at1.95A resolution. Mol Biol,231:445~458
Seiji I，Toshio O，Junichi K，Kiyoshi I and Kyozo H.1991. Amino acid sequences of nerve growth factorsderived from cobra venoms. FEBS,279(1):38~40
Seo K, Choi J, Park M，Rhee C.2001. Angiogenesis effects of nerve growth factor (NGF) on rat corneas. JVet Sci,2:125~130
Sewing A, Wiseman B, Lloyd A C and Land H.1997. High-intensity Raf signal causes cell cycle arrestmediated by p21Cip1. Mol. Cell Biol,17:5588~5597
Shamovsky I L，Ross G M，Riopelle R J and Weaver D F.1999. The interaction of neurotrophins with thep75NTR common neurotrophin receptor: a comprehensive molecular modeling study. Protein Sci,8:2223~2233
Shelley J A and David D W.2006. Clinical relevance of the neurotrophins and their receptors. ClinicalScience,110:175~191
Shibata H, Tokunaga T, Karasawa D, Hirota A, Nakayama M, Nozaki H, Tada T.1989. Isolation andcharacterization of new bitter diterpenoids from the fungus Sarcodon scabrosus. Agric Biol Chem,53(12):3373~3375
Shigeta K, Ootaki K, Tatemoto H, Nakanishi T, Inada A, Muto N.2002. Potentiation of nerve growthfactor-induced neurite outgrowth in PC12cells by a coptidis rhizome extract and protoberberinealkaloids. Bioscience, Biotechnology, and Biochemistry,66(11):2491~2494
Shiojima I, Walsh K.2006. Regulation of cardiac growth and coronary angiogenesis by the Akt/PKBsignaling pathway. Genes Dev,20:3347~3365
Shu X and Mendell L M.1999. Neurotrophins and hyperalgesia. Proc Natl Acad Sci USA,96:7693~7696
Smeyne R J, Klein R, Schnapp A, Long L K, Bryant S, Lewin A, Lira S A, Barbacid M.1994. Severesensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene. Nature,368:246~249
Snider D E J, Raviglione M and Kochi A.1994. Tuberculosis: pathogenesis, protection and control.In Tuberculosis: Pathogenesis, Protection and Control. Bloom, B. R., ed., Am. Soc. Microbiol,Washington, DC. pp.2-11
Solomon A, Aloe L, Pe'er J, Frucht Pery J, Bonini S, Levi Schaffer F.1998. Nerve growthfactorispreformed in and activates human peripheral blood eosinophils. JAl lergy Clin Immunol,102(3):454~460
Spivak-Kroizman T，Mohammadi M，Hu P，Jaye M，Schlessinger J and Lax I.1994. Point mutation in thefibroblast growth factor receptor eliminates phosphatidylinositol hydrolysis without affecting neuronaldifferentiation of PC12cells. J Biol Chem,269:14419~14423
Steinle J J and Granger H J.2003. Nerve growth factor regulates human choroidal, but not retinal,endothelial cell migration and proliferation. Auton Neurosci,108:57~62
Stephens R M, Loeb D M, Copeland T D, Pawson T, Greene L A, Kaplan D R.1994. Trk receptors useredundant signal transduction pathways involving SHC and PLC-gamma1to mediate NGF responses.Neuron,12:691~705
Suzuki E，Bogenmann H，Shimada D，Stram R C and Seeger R C.1993. Lack of high-affinity nerve growthfactor receptors in aggressive neuroblastomas. J. Natl. Cancer Inst.(Bethesda),85:377~384
Takeo C, Nakamura S, Tanaka T, Uchida D, Noguchi Y, NagaoT, Saito Y, Tatsuno I.2003. Rat cerebralendothelial cells express trk C and are regulated by neurotrophin-3. Biochem Biophys Res Commun,305:400~406
Tang W and Eisenbrand G.1992. Chinese drugs of plant origin: chemistry, pharmacology, and use intraditional and modern medicine. Berlin: Springer-Verlag,1992:817~847
Tessarollo L.1998. Pleiotropic functions of neurotrophins in development. Cytokine Growth Factor Rev,9:125~137
Tessarollo L, Tsoulfas P, Donovan M J, Palko M E, Blair-Flynn J, Hempstead B L, Parada L F.1997.Targeted deletion of all isoforms of the trkC gene suggests the use of alternate receptors by its ligandneurotrophin-3in neuronal development and implicates trkC in normal cardiogenesis. Proc Natl AcadSci USA,94:14776~14781
Traverse S, Seedorf K, Paterson H, Marshall C J, Cohen P and UIIrich A.1994. EGF triggers neuronaldifferentiation of PC12cells that overexpress the EGF receptor. Curr Biol,4:694~701
Traverse S, Gomez N, Paterson H, Marshall C and Cohen P.1992. Sustained activation of themitogen-activated protein (MAP) kinase cascade may be required for differentiation of PC12cells.Comparison of the effects of nerve growth factor and epidermal growth factor. Biochem J,288:351~355
Treanor J J，Buja R and Murphy B R.1991. Intragenic suppression of a deletion mutation of thenonstructural gene of an influenza A virus. J Virol,65:4204~4210
Treinies I, Paterson H F, Hooper S, Wilson R, Marshall C.1999. Activated MEK stimulates expression ofAP-1components independently of phosphatidylinositol3-kinase (PI3-kinase) but requires aPI3-kinase signal to stimulate DNA synthesis. Mol Cell Biol,19(1):321~329
Tsang C K，Kamei Y.2004. Sargaquinoic acid supports the survival of neuronal PC12D cells in a nervegrowth factor-independent manner. Eur JPharmacol,488:11~18
Tuszynski M H and Blesch A.2004. Nerve growth factor: From animal models of cholinergic neuronaldegeneration to gene therapy in AlzhelIIers disease. Prog Brain Res,146:441~449
Ulrich A, Gray A, Bereman C, Dull T J.1983. Human β-nerve Growth factor gene highly homologous tothat of mouse. Nature,303:821~825
Urfer R, Tsoulfas P, O’Connell L, Shelton D L, Parada L F, Presta L G.1995. An immunoglobulin-likedomain determines the specificity of neurotrophin receptors. Embo J,14:2795~2805
von Schack D, Casademunt E, Schweigreiter R, Meyer M, Bibel M and Dechant G.2001. Completeablation of the neurotrophin receptor p75NTR causes defects both in the nervous and the vascularsystem. Nat Neurosci,4:977~978
Wadhwa R, Yaguchi T, Taira K, Kaul S C.2003. Mortalin-MPD(mevalonate pyrophosphate decarboxylase)interactions and their role in control of cellular proliferaction. Biochem Biophys Res Commun,302:735~742
Wagner M, Kutash K, Duchnowski A J, Epstein M H, Sumi W C.2005. The children and youth we serve: Anational picture of the characteristics of students with emotional disturbances receiving specialeducation. Journal of Emotional and Behavioral Disorders,13(2):79~96
Walsh G S, Krol K M, Crutcher K A, Kawaja M D.1999. Enhanced neurotrophin-induced axon growth inmyelinated portions of the CNS in mice lacking the p75neurotrophin receptor. J Neurosci,19:4155~4l68
Wang S, Bray P, McCaffrey T, March K, Hempstead B L, Kraemer R.2000. p75(NTR) mediatesneurotrophin-induced apoptosis of vascular smooth muscle cells. Am J Pathol,157:1247~1258
Wang X, Bauer J H, Li Y, Shao Z, Zetoune F S, Cattaneo E, Vincenz C.2001. Characterization of ap75(NTR) apoptotic signaling pathway using a novel cellular model. J Biol Chem,276:33812~33820
Wang Z J, Nie B M, Chen H Z, Lu Y.2006. Panaxynol induces neurite outgrowth in PC12D cells viacAMP-and MAP kinase-dependent mechanisms. Chemico-Biological Interactions,159:58~64
Wehrman T, He X, Raab B, Dukipatti A, Blau H, Garcia K C.2007. Structural and mechanistic insightsinto nerve growth factor interactions with the Trk A and p75receptors. Neuron,53:25~38
Whitehouse P J，Price D L，Struble R G，Clark A W，Coyle J T and Delon M R.1982. Alzheimer’s diseaseand senile dementia：Loss of neurons in the basal forebrain. Science,215:1237~1239
Widenfalk J, Lundstromer K, Jubran M, Brene S, Olson L.2001. Neurotrophic factors and receptors in theimmature and adult spinal cord after mechanical injury or kainic acid. Neurosci,21(10):3457~3475
Wiesmann C and de Vos A M.2001. Nerve growth factor: structure and function. Cell Mol Life Sci,58:748~759
Wilkie N，Wingrove P B，Bilsland J G，Young L, Harper S J, Hefti F, Ellis S, Pollack S J.2001. Thenon-peptidyl fungal metabolite L-783,281activates TRKneurotrophin receptors. J Neurochem,78:1135~1145
Williams B J，Eriksdotte-Jonhagen M，Granholm A C.2006. Nerve growth factor in treatment andpathogenesis of Alzheimer’s disease. Prog Neurobiol,80:114~128
Wolf D E, McKinnon-Thompson C, Daou M C, Stephens R M, Kaplan D R, Ross A H.1998. Mobility ofTrkA is regulated by phosphorylation and interation with the low affinity NGF receptor. Biochem istry,37(9):3178~3186
Woods D，Parry D，Cherwinski H，Bosch E，Lees E，McMahon M.1997. Raf-induced proliferation orcell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1. Mol CellBiol,17:5598~5611
Woolf C J，Safieh-Garabedian B，Ma Q P，Crilly P，Winter J.1994. Nerve growth factor contributes to thegeneration of inflammatory sensory hypersensitivity. Neuroscience,62:327~331
Yaar M，Grossman K，Eller M and Gilchrest B A.1991. Evidence for nerve growth factor-mediatedparacrine effects in human epidermis. J Cell Biol,115:821~828
Yamashita A, Chang T C, Yamashita Y, Zhu W, Zhong Z, Chen C Y, Shyu A B.2005. Concerted action ofpoly (A) nucleases and decapping enzyme in mammalian mRNA turnover. Nat Struct Mol Biol,12:1054~1063
Yang Y J, Lee H J, Choi D H, Huang H S, Lim S C, Lee M K.2008. Effect of scoparone on neuriteoutgrowth in PC12cells. Neuroscience Letters,440:14~18
Yano M, Katayose Y, Ashikari M, Yamanouchi U, Monna L, Fuse T, Baba T, Yamamoto K, Umehara Y,Nagamura Y.2000. Hd1, a major photoperiod sensitivity quantitative trait locus in rice, is closelyrelated to the arabidopsis flowering time gene CONSTANS. Plant Cell,12:2473~2484
Yano H and Chao M.2000. Neurotrophin receptor structure and interactions. Pharm Acta Helv,74:253~260
Yip H K, Gmfstein B.1982. Efect of nerve growth factor on regeneration of goldfish optic axons. BrainRes,238(2):329~339
Yoon P W, Freeman S B, Sherman S L, Taft L F, Gu Y, Pettay D, Flanders W D, Khoury M J and HassoldT J.1996. Advanced maternal age and the risk of Down Syndrome characterized by the meiotic stageof the chromosome error: a population-based study. Amer J Hum Genet,58:628~633
Yoon S O, Casaccia-Bonnefil P, Carter B, Chao M V.1998. Competitive signaling between TrkA and p75nerve growth factor receptors determines cell survival. J Neurosci,18:3273~3281
Young M K, Yu M H, Yong C J, Lian Y S, Yong S L, Hye J K, Han G S, Jae S C, Yeong S K, Sam S K,Jae H L, Ki C C.2009. Palmatine from Coptidis rhizoma reduces ischemia-reperfusion-mediatedacute myocardial injury in the rat. Food and Chemical Toxicology,47:2097~2102
Zhang L，Peng S P，Han R，Qiu J H, Gu Z l, Qin Z H.2005. A lipophilic fraction of Ganoderma lueidumpromotes PC12differentiation. Chin Pharmacol Bull,21:662~667
Zhou M, Xu Y J, Xiong S D, Zhao J P, Ni W, Zhang Z X.2003．The expression of nerve growth factor ininflammatory cells of induced sputum from patients with asthma. Chinese Journal of InternalMedicine,42(11):764~767
Zhang W, Peng F F, Zhang B F, Shen H, Wu S B, Wu D C.2005. Role of ERK in PC12cells Induced bydifferentiation NGF. Basic&Clinical Medicine,25(3):227~231
Zhang Y, Pei L, Gao L, Huang Q, Qi J.2011. A neuritogenic compound from Tremella fuciformis.Zhongguo Zhong Yao Za Zhi,36(17):2358~2360