关于阿尔茨海默症的突触可塑性改变和中药治疗研究进展
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摘要
阿尔茨海默症(Alzheimer’s disease, AD)与突触的功能改变密切相关,尤其是作为疾病早期的病理改变,而且对研究记忆的形成与神经退行性改变的机制相当重要。探究影响突触功能与可塑性的病理因素,对患者恢复认知功能有重要作用,同时也可指明药物研发方向,为药物开发提供新的靶点。中药具有不良反应小、多靶点、多环节的优点,我国中药资源丰富,从中药成分中开发新的改善突触功能的抗AD药物有着重要的意义。对阿尔茨海默症中影响突触可塑性改变的病理因素及可改善突触功能的抗AD中药研究进行综述。
Alzheimer's disease is closely related with synaptic function alteration, particularly as an early pathological alteration in the disease. It also plays a significant role in investigations of memory formation and the mechanism of neurodegeneration. Searching for pathological factors that affect synaptic function and plasticity, will have significant meaning for restoring cognitive function to find out new target and guide the direction of drug development. Traditional Chinesemedicine has small toxic side effect, with multi-target, multi-channeland multi-link effect of functions and characteristics. Ingredients from Chinese medicine were extractedand developedto exploit a new drug to improve synaptic activity. This article summarizes and reviews pathological factor of synaptic plasticity deficits, and the Chinese medicine research with synaptic protective effect.
Alzheimer's disease is closely related with synaptic function alteration, particularly as an early pathological alteration in the disease. It also plays a significant role in investigations of memory formation and the mechanism of neurodegeneration. Searching for pathological factors that affect synaptic function and plasticity, will have significant meaning for restoring cognitive function to find out new target and guide the direction of drug development. Traditional Chinesemedicine has small toxic side effect, with multi-target, multi-channeland multi-link effect of functions and characteristics. Ingredients from Chinese medicine were extractedand developedto exploit a new drug to improve synaptic activity. This article summarizes and reviews pathological factor of synaptic plasticity deficits, and the Chinese medicine research with synaptic protective effect.
引文
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[29] Yamakuni T, Nakajima A. Preventive action of nobiletin, a constituent of AURANTII NOBILIS PERICARPIUM with anti-dementia activity, against amyloid-beta peptide-induced neurotoxicity expression and memory impairment[J]. The Pharmaceutical Society of Japan, 2010, 130(4): 517-520.
[30] Zhang L, Shen C, Chu J, et al. Icariin decreases the expression of APP and BACE-1 and reduces the β-amyloid burden in an APP transgenic mouse model of Alzheimer’s disease[J]. Int J Biol Sci, 2014, 10(2): 181-191.
[31] Zhang D, ZheWang, Sheng C, et al. Icariin Prevents Amyloid Beta-Induced Apoptosis via the PI3K/Akt Pathway in PC-12 Cells[J]. Evid Based Complement Alternat Med, 2015.
[32] Sheng C, Xu P, Zhou K. Icariin Attenuates Synaptic and Cognitive Deficits in an Aβ 1-42-Induced Rat Model of Alzheimer’s Disease[J]. Biomed Res Int, 2017,2017:1-12.
[33] Chen Y, Han S, Huang X, et al. The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3× Tg-AD Mice[J]. Int J Mol Sci, 2016, 17(2):163.
[34] Manavalan A, Ramachandran U, Sundaramurthi H, et al. Gastrodia elata Blume (tianma) mobilizes neuro-protective[J]. Int J Biochem Mol Biol, 2012, 3(2): 219-241.
[35] Shi J, Tian J, Zhang X, et al. A combination extract of ginseng, epimedium, polygala, and tuber curcumae increases synaptophysin expression in APPV717I transgenic mice[J]. Chin Med, 2012, 7(1): 13.
[2] Chakroborty S, Kim J2, Schneider C, et al. Nitric oxide signaling is recruited as a compensatory mechanism for sustaining synaptic plasticity in Alzheimer’s disease mice[J]. 2015, 35(17): 6893-6902.
[3] Blanchard J, Wanka L, Tung YC, et al. Pharmacologic reversal of neurogenic and neuroplastic abnormalities and cognitive impairments without affecting Aβ and tau pathologies in 3xTg-AD mice[J]. Acta Neuropathol, 2010, 120(5): 605-621.
[4] RS1 W, DF2 C, Whitehead SN. Assessing the Effects of Acute Amyloid β Oligomer Exposure in the Rat[J]. Int J Mol Sci, 2016, 17(9): 1390.
[5] Cissé M, Halabisky B, Harris J, et al. Reversing EphB2 depletion rescues cognitive functions in Alzheimer model[J]. Nature, 2011, 469(7328): 47-52.
[6] Shi XD, Sun K, Hu R, et al. Blocking the Interaction between EphB2 and ADDLs by a Small Peptide Rescues Impaired Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer’s Disease[J]. J Neurosci, 2016, 36(47): 11959-11973.
[7] Hu R, Wei P, Jin L, et al. Overexpression of EphB2 in hippocampus rescues impaired NMDA receptors trafficking and cognitive dysfunction in Alzheimer model[J]. Cell Death Dis, 2017, 8(3): e2717.
[8] Laurén J, Gimbel DA, Nygaard HB, et al. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers[J]. Nature, 2009, 457(7233): 1128-1132.
[9] Arrieta-Cruz I, Gutiérrez-Juárez R. The Role of Insulin Resistance and Glucose Metabolism Dysregulation in the Development of Alzheimer’s Disease[J]. Rev Inves Clin, 2016, 68: 53-58.
[10] Kandel ER. The molecular biology of memory storage: a dialogue between genes and synapses[J]. Science, 2001, 294(5544): 1030-1038.
[11] Gr?ff J, Kim D, Dobbin MM, et al. Epigenetic regulation of gene expression in physiological and pathological brain processes[J]. Physiol Rev, 2011, 91(2): 603-649.
[12] 王晓良. 应用分子药理学[M]. 北京:中国协和医科大学出版社, 2015:95-99.
[13] Guan JS, Haggarty SJ, Giacometti E, et al. HDAC2 negatively regulates memory formation and synaptic plasticity[J]. Nature, 2009, 459(7243): 55-60.
[14] Gr?ff J, Rei D, Guan JS, et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain[J]. Nature, 2012, 483(7388): 222-226.
[15] Manoa T, Nagatab K. Neuron-specific methylome analysis reveals epigenetic[J]. Proc Natl Acad Sci USA, 2017, 114(45): E9645-E9654.
[16] Gasiorowski K, Brokos B1, Leszek J, et al. Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important[J]. Curr Top Med Chem, 2017(17): 1429-1437.
[17] Ashraf GM, Greig NH, Khan TA, et al. Protein misfolding and aggregation in Alzheimer’s disease and type 2 diabetes mellitus[J]. CNS Neurol Disord Drug Targets, 2014,13(7):1280-1293.
[18] Walker JM, Harrison FE. Shared Neuropathological Characteristics of Obesity, Type 2 Diabetes and Alzheimer’s Disease: Impacts on Cognitive Decline[J]. Nutrients, 2015, 7(9): 7332-7357.
[19] Pascual-Lucas M, Viana dSS, Di SM, et al. Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice[J]. EMBO Mol Med, 2014, 6(10): 1246-1262.
[20] Lim CS, Alkon DL. Inhibition of coactivator-associated arginine methyltransferase 1 modulates dendritic arborization and spine maturation of cultured hippocampal neurons[J]. J Biol Chem, 2017, 292(15): 6402-6413.
[21] Sancheti H, Akopian G, Yin F, et al. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer’s disease[J]. PLoS One, 2013, 8(7): e69830.
[22] Wu J, Liu C1, Zhang L. Histone deacetylase-2 is involved in stress-induced cognitive impairment via histone deacetylation and PI3K/AKT signaling pathway modification[J]. Mol Med Rep, 2017, 16(2): 1846-1854.
[23] Baazaoui N, Iqbal K. Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound[J]. Alzheimers Res Ther, 2017, 9(1): 45.
[24] Panatier A1, Robitaille R. Astrocytic mGluR5 and the tripartite synapse[J]. Neuroscience, 2016, 323: 29-34.
[25] Henneberger C, Papouin T, Oliet SH, et al. Long term potentiation depends on release of D-serine from[J]. Nature, 2010, 463(7278): 232-236.
[26] Wei S. Potential therapeutic action of natural products from traditional Chinese medicine on Alzheimer’s disease animal models targeting neurotrophic factors[J]. Fundam Clin Pharmacol, 2016, 30(6): 490-501.
[27] Sreenivasmurthy SG, Liu JY, Song JX. Neurogenic Traditional Chinese Medicine as a Promising Strategy for the Treatment of Alzheimer’s Disease[J]. Int J Mol Sci, 2017, 18(2):272.
[28] Yan S, Li Z, Li H, et al. Notoginsenoside R1 increases neuronal excitability and ameliorates synaptic and memory dysfunction following amyloid elevation[J]. Sci Rep, 2014, 4: 6352.
[29] Yamakuni T, Nakajima A. Preventive action of nobiletin, a constituent of AURANTII NOBILIS PERICARPIUM with anti-dementia activity, against amyloid-beta peptide-induced neurotoxicity expression and memory impairment[J]. The Pharmaceutical Society of Japan, 2010, 130(4): 517-520.
[30] Zhang L, Shen C, Chu J, et al. Icariin decreases the expression of APP and BACE-1 and reduces the β-amyloid burden in an APP transgenic mouse model of Alzheimer’s disease[J]. Int J Biol Sci, 2014, 10(2): 181-191.
[31] Zhang D, ZheWang, Sheng C, et al. Icariin Prevents Amyloid Beta-Induced Apoptosis via the PI3K/Akt Pathway in PC-12 Cells[J]. Evid Based Complement Alternat Med, 2015.
[32] Sheng C, Xu P, Zhou K. Icariin Attenuates Synaptic and Cognitive Deficits in an Aβ 1-42-Induced Rat Model of Alzheimer’s Disease[J]. Biomed Res Int, 2017,2017:1-12.
[33] Chen Y, Han S, Huang X, et al. The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3× Tg-AD Mice[J]. Int J Mol Sci, 2016, 17(2):163.
[34] Manavalan A, Ramachandran U, Sundaramurthi H, et al. Gastrodia elata Blume (tianma) mobilizes neuro-protective[J]. Int J Biochem Mol Biol, 2012, 3(2): 219-241.
[35] Shi J, Tian J, Zhang X, et al. A combination extract of ginseng, epimedium, polygala, and tuber curcumae increases synaptophysin expression in APPV717I transgenic mice[J]. Chin Med, 2012, 7(1): 13.