摘要
脑源性神经营养因子(BDNF)是脑组织中占主导地位的神经营养因子,在分化、再生和可塑性机制中起着至关重要的作用。BDNF与其结合高亲和力的肌球蛋白相关激酶B(TrkB)受体导致TrkB磷酸化,从而激活神经细胞内三条重要的下游信号级联。包括磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)、磷脂酶C-γ(PLCγ)和有丝分裂原活化蛋白激酶/细胞外信号相关激酶(MAPK/ERK)通路。语音转写其中N是由cAMP反应元件结合蛋白(CrEB)转录因子调控的,可上调基因的表达。在这篇综述中,我们尝试探讨bdnf an的作用。d与精神分裂症(SCZ)、阿尔茨海默氏病(AD)和帕金森病(PD)易感性相关的通路。此外,我们还讨论了BDNF信号通路的功能障碍及其治疗。BDNF在这些疾病治疗中的作用。本文综述了多种治疗策略,包括BDNF基因治疗、BDNF表达细胞移植、表观遗传操作等。同时也有脑实质内BDNF蛋白的注入。本综述旨在通过回顾最近有关BDNF的研究,以及在上述任何一中疾病中检查BDNF通路的细节来实现这些目标。
关键词: 基因传递,BDNF,PLCγ,MAPK/ERK,敏感性,PI3K/AKT。
Current Gene Therapy
Title:Dysfunction in Brain-Derived Neurotrophic Factor Signaling Pathway and Susceptibility to Schizophrenia, Parkinson’s and Alzheimer’s Diseases
Volume: 18 Issue: 1
关键词: 基因传递,BDNF,PLCγ,MAPK/ERK,敏感性,PI3K/AKT。
摘要: Brain-Derived Neurotrophic Factor (BDNF) is a dominant neurotrophic factor in the brain which plays a crucial role in differentiation, regeneration and plasticity mechanisms. Binding of the BDNF to its high-affinity Tropomyosin-related kinase B (TrkB) receptor leads to phosphorylation of TrkB, thus activating the three important downstream intracellular signaling cascades within the neural cells including phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), Phospholipase C-γ (PLCγ), and mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK) pathways. Transcription of these pathways is regulated by cAMP Response Element-Binding protein (CREB) transcription factor, which can upregulate gene expression. In this review, we attempted to explore the role of BDNF and its associated pathways in susceptibility to Schizophrenia (Scz), Alzheimer's (AD), and Parkinson's (PD) diseases. Furthermore, we discuss dysfunction in BDNF signaling pathway and the therapeutic potential of BDNF in the treatment of these disorders. The review covers various therapeutic strategies including BDNF gene therapy, transplantation of BDNFexpressing cell grafts, epigenetic manipulation, and intraparenchymal BDNF protein infusion as well. This review seeks to achieve these goals by reviewing recent studies on BDNF and examining the details of BDNF pathway in any of the above-mentioned diseases.
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Dysfunction in Brain-Derived Neurotrophic Factor Signaling Pathway and Susceptibility to Schizophrenia, Parkinson’s and Alzheimer’s Diseases, Current Gene Therapy 2018; 18 (1) . https://dx.doi.org/10.2174/1566523218666180302163029
DOI https://dx.doi.org/10.2174/1566523218666180302163029 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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