脑源性神经营养因子在阿尔茨海默症中作用研究进展
Research Progress of Brain-Derived Neurotrophic Factor in Alzheimer’s Disease
摘要: 阿尔茨海默症(AD)是引起老年痴呆的主要原因,其病理特征包括淀粉样斑块和神经纤维缠结。AD广泛的神经元和突触丢失引起记忆和认知功能进行性减退。脑源性神经营养因子(BDNF)是成人大脑内分布最广泛的神经营养因子。BDNF在记忆获得和巩固的细胞生物学基础突触发生及突触可塑性中发挥关键作用。研究表明,BDNF可能成为AD的生物标记和治疗靶标。本文主要对BDNF在AD中发挥的作用及其治疗策略进行综述。
Abstract: Alzheimer’s disease (AD) is one of the most common causes of dementia in the elderly. It is char-acterized by the accumulation of Aβ plaques and neurofibrillary tangles, which are accompanied by widespread neuronal and synaptic loss, causing progressive loss of memory and cognitive function. Brain-derived neurotrophic factor (BDNF) is the most widely distributed NTs in adult brain and is a key molecule in the maintenance of synaptic plasticity and synaptogenesis, which is the cellular biological basis of memory acquisition and consolidation. BDNF may play a potential role in the pathogenesis of Alzheimer’s disease. The review provides the role and therapeutic strategy of brain-derived neurotrophic factor in Alzheimer’s disease in major.
文章引用:冯晓文, 何玲. 脑源性神经营养因子在阿尔茨海默症中作用研究进展[J]. 药物资讯, 2017, 6(2): 31-35. https://doi.org/10.12677/PI.2017.62006

参考文献

[1] Blennow, K., De Leon, M.J., et al. (2006) Alzheimer’s Disease. Lancet, 368, 387-403. [Google Scholar] [CrossRef
[2] Ties, W. and Bleiler, L. (2013) Alzheimer’s Association. 2013 Alz-heimer’s Disease Facts and Figures. Alzheimers Dement, 9, 208-245. [Google Scholar] [CrossRef] [PubMed]
[3] Huang, E.J. and Reichardt, L.F. (2001) Neurotrophins: Roles in Neuronal Development and Function. Annual Review of Neuroscience, 24, 677-736. [Google Scholar] [CrossRef] [PubMed]
[4] Minichiello, L. (2009) TrkB Signalling Pathways in LTP and Learning. Nature Reviews Neuroscience, 10, 850-860. [Google Scholar] [CrossRef] [PubMed]
[5] Koponen, E., Voikar, V., et al. (2004) Transgenic Mice Overexpressing the Full-Length Neurotrophin Receptor TrkB Exhibit Increased Activation of the TrkB-PLC Gamma Pathway, Reduced Anxiety, and Facilitated Learning. Molecular and Cellular Neuroscience, 26, 166-181. [Google Scholar] [CrossRef] [PubMed]
[6] Mattson, M.P., Maudsley, S. and Martin, B. (2004) A Neural Signaling Triumvirate That Influences Ageing and Age Related Disease: Insulin/IGF-1, BDNF and Serotonin. Ageing Research Reviews, 3, 445-464. [Google Scholar] [CrossRef] [PubMed]
[7] Bekinschtein, P., Cammarota, M., et al. (2008) BDNF Is Essential to Promote Persistence of Long-Term Memory Storage. Proceedings of the National Academy of Sciences USA, 105, 2711-2716. [Google Scholar] [CrossRef] [PubMed]
[8] Zuccato, C. and Cattaneo, E. (2009) Brain-Derived Neurotrophic Factor in Neurodegenerative Diseases. Nature Reviews Neurology, 5, 311-322. [Google Scholar] [CrossRef] [PubMed]
[9] Castello, N.A., Green, K.N., et al. (2012) Genetic Knockdown of Brain-Derived Neurotrophic Factor in 3xTg-AD Mice Does Not Alter Abeta or Tau Pathology. PLoS One, 7, 539-566. [Google Scholar] [CrossRef] [PubMed]
[10] Jimenez, S., Torres, M., et al. (2011) Age-Dependent Accumulation of Soluble Amyloid β (Aβ) Oligomers Reverses the Neuroprotective Effect of Soluble Amyloid Precursor Protein-α (sAPPα) by Modulating Phosphatidylinositol 3-Kinase (PI3K)/Akt-GSK-3β Pathway in Alzheimer Mouse Model. Journal of Biological Chemistry, 286, 18414- 18425. [Google Scholar] [CrossRef
[11] Huang, W.D., Cao, J., et al. (2015) AMPK Plays a Dual Role in Regulation of CREB/BDNF Pathway in Mouse Primary Hippocampal Cells. Journal of Molecular Neuroscience, 56, 782-788. [Google Scholar] [CrossRef] [PubMed]
[12] Zeng, Y., Zhao, D., et al. (2010) Neurotrophins Enhance CaMKII Activity and Rescue Amyloid-β-Induced Deficits in Hippocampal Synaptic Plasticity. Journal of Alzheimer’s Disease, 21, 823-831. [Google Scholar] [CrossRef
[13] Poon, W.W., Blurton, M., et al. (2011) Beta-Amyloid Impairs Axonal BDNF Retrograde Trafficking. Neurobiology of Aging, 32, 821-833. [Google Scholar] [CrossRef] [PubMed]
[14] Holback, S., Adlerz, L., et al. (2005) Increased Processing of APLP2 and APP with Concomitant Formation of APP Intracellular Domains in BDNF and Retinoic Acid Differentiated Human Neuroblastoma Cells. Journal of Neurochemistry, 95, 1059-1068. [Google Scholar] [CrossRef] [PubMed]
[15] Elliott, E., Atlas, R., Lange, A., et al. (2005) Brain-Derived Neurotrophic Factor Induces a Rapid Dephosphorylation of Tau Protein through a PI-3 Kinase Signaling Mechanism. European Journal of Neuroscience, 22, 1081-1089. [Google Scholar] [CrossRef] [PubMed]
[16] Shankar, G.M. and Walsh, D.M. (2009) Alzheimer’s Disease: Synaptic Dysfunction and Abeta. Molecular Neurodegeneration, 4, 48. [Google Scholar] [CrossRef] [PubMed]
[17] Selkoe, D.J. (2002) Alzheimer’s Disease Is a Synaptic Failure. Science, 298, 789-791. [Google Scholar] [CrossRef] [PubMed]
[18] Fritsch, B., et al. (2010) Direct Current Stimulation Promotes BDNF-Dependent Synaptic Plasticity: Potential Implications for Motor Learning. Neuron, 66, 198-204. [Google Scholar] [CrossRef] [PubMed]
[19] Zeng, Y., Zhao, D., et al. (2010) Neurotrophins Enhance CaMKII Activity and Rescue Amyloid-Beta-Induced Deficits in Hippocampal Synaptic Plasticity. Journal of Alzheimer’s Disease, 21, 823-831. [Google Scholar] [CrossRef
[20] Ninan, I., Bath, K.G., et al. (2010) The BDNF Val66Met Polymorphism Impairs NMDA Receptor-Dependent Synaptic Plasticity in the Hippocampus. Journal of Neuroscience, 30, 8866-8870. [Google Scholar] [CrossRef
[21] Autio, H., Matlik, K., et al. (2011) Acetylcholinesterase Inhibitors Rapidly Activate Trk Neurotrophin Receptors in the Mouse Hippocampus. Neuropharmacology, 61, 1291-1296. [Google Scholar] [CrossRef] [PubMed]
[22] Wu, H.M., Tzeng, N.S., et al. (2009) Novel Neuroprotective Mechanisms of Memantine: Increase in Neurotrophic Factor Release from Astroglia and Anti-Inflammation by Preventing Microglial Activation. Neuropsychopharmacology, 34, 2344-2357. [Google Scholar] [CrossRef] [PubMed]
[23] Luo, J., Zhang, L., et al. (2013) Neotrofin Reverses the Effects of Chronic Unpredictable Mild Stress on Behavior via Regulating BDNF, PSD-95 and Synaptophysin Expression in Rat. Behavioural Brain Research, 253, 48-53. [Google Scholar] [CrossRef] [PubMed]
[24] Hoppe, J.B., Coradini, K., et al. (2013) Free and Nanoencapsulated Curcumin Suppress Beta-Amyloid-Induced Cognitive Impairments in Rats: Involvement of BDNF and Akt/GSK-3beta Signaling Pathway. Neurobiology of Learning and Memory, 106, 134-144. [Google Scholar] [CrossRef] [PubMed]
[25] Nagahara, A.H., Mateling, M., et al. (2013) Early BDNF Treatment Ameliorates Cell Loss in the Entorhinal Cortex of APP Transgenic Mice. Journal of Neuroscience, 33, 15596-15602. [Google Scholar] [CrossRef
[26] Zhang, Z., Liu, X., et al. (2014) 7,8-Dihydroxyflavone Prevents Synaptic Loss and Memory Deficits in a Mouse Model of Alzheimer’s Disease. Neuropsychopharmacology, 39, 638-650. [Google Scholar] [CrossRef] [PubMed]
[27] Blurton, J.M., Kitazawa, M., et al. (2009) Neural Stem Cells Improve Cognition via BDNF in a Transgenic Model of Alzheimer Disease. Proceedings of the National Academy of Sciences, 106, 13594-13599. [Google Scholar] [CrossRef] [PubMed]
[28] Shin, M.K., Kim, H.G., et al. (2014) Neuropep-1 Ameliorates Learning and Memory Deficits in an Alzheimer’s Disease Mouse Model, Increases Brain-Derived Neurotrophic Factor Expression in the Brain, and Causes Reduction of Amyloid Beta Plaques. Neurobiology of Aging, 35, 990-1001. [Google Scholar] [CrossRef] [PubMed]
[29] Hsiao, Y.H., Hung, H.C., et al. (2014) Social Interaction Rescues Memory Deficit in an Animal Model of Alzheimer’s Disease by Increasing BDNF-Dependent Hippocampal Neurogenesis. Journal of Neuroscience, 34, 16207-16219. [Google Scholar] [CrossRef
[30] Coelho, F.G., Vital, T.M., et al. (2014) Acute Aerobic Exercise Increases Brain-Derived Neurotrophic Factor Levels in Elderly with Alzheimer’s Disease. Journal of Alzheimer’s Disease, 39, 401-408.