不同形态脑源性神经营养因子与阿尔茨海默病关系研究进展
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摘要
阿尔茨海默病(AD)是一种常见的中枢神经系统变性疾病,是老年痴呆人群的主要病因。脑源性神经营养因子(BDNF)是神经营养蛋白家族的重要成员。BDNF及其前体蛋白脑源性神经营养因子前体(proBDNF)、脑源性神经营养因子前肽(pBDNF)在AD发病机制中起着重要作用。现对BDNF、proBDNF及pBDNF的表达、功能及其与AD之间的关系进行综述如下。
引文
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[25]LIM J Y,REIGHARD C P,CROWTHER D C.The prodomains of neurotrophins,including BDNF,are linked to Alzheimer′s disease through a toxic synergy with Aβ[J].Hum Mol Genet,2015,24(14):3929-3938.
[2]DIENI S,MATSUMOTO T,DEKKERS M,et al.BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain neurons[J].J Cell Biol,2012,196(6):775-788.
[3]YANG J,HARTE-HARGROVE L C,SIAO C J,et al.proBDNF negatively regulates neuronal remodeling,synaptic transmission,and synaptic plasticity in hippocampus[J].Cell Rep,2014,7(3):796-806.
[4]KOJIMA M,MIZUI T.BDNF propeptide:a novel modulator of synaptic plasticity[J].Vitam Horm,2017,104:19-28.
[5]LU B,NAGAPPAN G,GUAN X,et al.BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases[J].Nat Rev Neurosci,2013,14(6):401-416.
[6]JI M,YUAN H,YUAN S,et al.The p75neurotrophin receptor might mediate sepsis-induced synaptic and cognitive impairments[J].Behav Brain Res,2018,347:339-349.
[7]ZHOU L,XIONG J,RUAN C S,et al.ProBDNF/p75NTR/sortilin pathway is activated in peripheral blood of patients with alcohol dependence[J].Transl Psychiatry,2018,7(11):2.
[8]XU Z Q,SUN Y,LI H Y,et al.Endogenous proBDNF is a negative regulator of migration of cerebellar granule cells in neonatal mice[J].Eur J Neurosci,2011,33(8):1376-1384.
[9]YANG B,QIN J,NIE Y,et al.Brain-derived neurotrophic factor propeptide inhibits proliferation and induces apoptosis in C6glioma cells[J].Neuroreport,2017,28(12):726-730.
[10]GUO J,JI Y,DING Y,et al.BDNF pro-peptide regulates dendritic spines via caspase-3[J].Cell Death Dis,2016,7:e2264.
[11]HACHISU M,KONISHI K,HOSOI M,et al.Beyond the hypothesis of serum anticholinergic activity in alzheimer′s disease:acetylcholine neuronal activity modulates brainderived neurotrophic factor production and inflammation in the brain[J].Neurodegener Dis,2015,15(3):182-187.
[12]ROSA E,FAHNESTOCK M.CREB expression mediates amyloidβ-induced basal BDNF downregulation[J].Neurobiol Aging,2015,36(8):2406-2413.
[13]JERNIMO-SANTOS A,FONSECA-GOMES J,GUIMARES D A,et al.Brain-derived neurotrophic factor mediates neuroprotection against Aβ-induced toxicity through a mechanism Independent on adenosine 2A receptor activation[J].Growth Factors,2015,33(4):298-308.
[14]BUCHMAN A S,YU L,BOYLE P A,et al.Higher brain BDNF gene expression is associated with slower cognitive decline in older adults[J].Neurology,2016,86(8):735-741.
[15]ROSA E,MAHENDRAM S,KE Y D,et al.Tau downregulates BDNF expression in animal and cellular models of Alzheimer′s disease[J].Neurobiol Aging,2016,48:135-142.
[16]JIAO S S,SHEN L L,ZHU C,et al.Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer′s disease[J].Transl Psychiatry,2016,6(10):e907.
[17]ADAMCZUK K,DE WEER A S,NELISSEN N,et al.Polymorphism of brain derived neurotrophic factor influencesβamyloid load in cognitively intact apolipoprotein Eε4carriers[J].Neuroimage Clin,2013,2:512-520.
[18]LIM Y Y,HASSENSTAB J,CRUCHAGA C,et al.BDNF Val66Met moderates memory impairment,hippocampal function and tau in preclinical autosomal dominant Alzheimer′s disease[J].Brain,2016,139(Pt 10):2766-2777.
[19]DINIZ C R,CASAROTTO P C,RESSTEL L,et al.Beyond good and evil:A putative continuum-sorting hypothesis for the functional role of proBDNF/BDNF-propeptide/mBDNF in antidepressant treatment[J].Neurosci Biobehav Rev,2018,90:70-83.
[20]BAI Y Y,RUAN C S,YANG C R,et al.ProBDNF signaling regulates Depression-Like behaviors in rodents under chronic stress[J].Neuropsychopharmacology,2016,41(12):2882-2892.
[21]CHEN J,LI C R,YANG H,et al.proBDNF attenuates hippocampal neurogenesis and induces learning and memory deficits in aged mice[J].Neurotox Res,2016,29(1):47-53.
[22]CHEN J,ZHANG T,JIAO S,et al.proBDNF accelerates brain amyloid-βdeposition and learning and memory impairment in APPswePS1dE9transgenic mice[J].J Alzheimers Dis,2017,59(3):941-949.
[23]KAILAINATHAN S,PIERS T M,YI J H,et al.Activation of a synapse weakening pathway by human Val66but not Met66pro-brain-derived neurotrophic factor(proBDNF)[J].Pharmacol Res,2016,104:97-107.
[24]YANG B,REN Q,ZHANG J C,et al.Altered expression of BDNF,BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders:rethinking the brain-liver axis[J].Transl Psychiatry,2017,7(5):e1128.
[25]LIM J Y,REIGHARD C P,CROWTHER D C.The prodomains of neurotrophins,including BDNF,are linked to Alzheimer′s disease through a toxic synergy with Aβ[J].Hum Mol Genet,2015,24(14):3929-3938.