Brain-derived neurotrophic factor Regulation, effects, and potential clinical relevance
Brain-derived neurotrophic factor Regulation, effects, and potential clinical relevance
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DOI：
10.1212/wnl.0000000000001507
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发表时间：
2015-04-21
期刊：
影响因子：
9.9
通讯作者：
Benarroch, Eduardo E.
中科院分区：
文献类型：
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作者：
Benarroch, Eduardo E.
脑源性神经营养因子（BDNF）是中枢神经系统中最普遍存在和研究最深入的神经营养因子家族成员。BDNF的转录调控是复杂的，涉及表观遗传控制和转录因子。BDNF是响应于神经元活动而按需产生的，其来自通过分泌途径转运和加工的前体BDNF原。成熟BDNF的作用由原肌球蛋白相关激酶B（Trk B，酪氨酸激酶B）受体介导，其触发磷酸化级联反应，促进蛋白质合成、轴突生长、树突成熟、使用依赖性突触可塑性和神经保护。相反，pro-BDNF与常见的神经营养因子受体p75（NTR）结合并促进细胞凋亡。BDNF也可以从小胶质细胞中释放，并且可以双向影响CNS中的抑制性神经传递。BDNF的表观遗传控制、转运或信号传导的紊乱可能导致多种神经和精神疾病，包括阿尔茨海默病（AD）、亨廷顿病（HD）、脊髓小脑共济失调6型（SCA 6）、神经性疼痛、Rett综合征和抑郁症、精神分裂症和药物成瘾。最近有几篇关于这些主题的评论。（1-20）
Brain-derived neurotrophic factor (BDNF) is the most ubiquitous and intensively studied member of the family of neurotrophins in the CNS. The transcriptional regulation of BDNF is complex and involves both epigenetic control and transcription factors. BDNF is produced on demand in response to neuronal activity from a precursor pro-BDNF that is transported and processed via the secretory pathway. The effects of mature BDNF are mediated by the tropomyosin-related kinase B (TrkB, tyrosine kinase B) receptor, which triggers phosphorylation cascades that promote protein synthesis, axonal growth, dendritic maturation, use-dependent synaptic plasticity, and neuroprotection. In contrast, pro-BDNF binds to the common neurotrophin receptor p75(NTR) and promotes apoptosis. BDNF can also be released from microglia and may bidirectionally affect inhibitory neurotransmission in the CNS. Disturbances in epigenetic control, transport, or signaling by BDNF may contribute to a variety of neurologic and psychiatric disorders, including Alzheimer disease (AD), Huntington disease (HD), spinocerebellar ataxia type 6 (SCA6), neuropathic pain, Rett syndrome, and depression, schizophrenia, and drug addiction. There are several recent reviews on these subjects.(1-20