Implications of GABAergic Neurotransmission in Alzheimer's Disease.
Implications of GABAergic Neurotransmission in Alzheimer's Disease.
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DOI：
10.3389/fnagi.2016.00031
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发表时间：
2016
影响因子：
4.8
通讯作者：
Zheng H
中科院分区：
文献类型：
--
作者：
Li Y;Sun H;Chen Z;Xu H;Bu G;Zheng H
阿尔茨海默病（Alzheimer's disease，AD）的病理特征是β-淀粉样肽（Aβ）的沉积和由过度磷酸化的tau蛋白组成的神经元缠结（NFT）的积累。不管病理学特征如何，突触功能障碍被广泛接受为AD的因果事件。在中枢神经系统（CNS）中的两种主要类型的突触中：多巴胺能和GABA能，其分别提供兴奋性和抑制性输出，大量的数据暗示在疾病进展期间受损的多巴胺能系统。然而，新出现的证据支持这样的观点，即破坏默认神经元网络是记忆受损的基础，并且GABA能回路的改变，无论是起主要作用还是作为对兴奋性毒性的代偿反应，也可能通过破坏整体网络功能而导致AD。本文综述了Aβ、tau蛋白和载脂蛋白E4（apoE 4）（迟发性AD的主要遗传危险因子）在GABA能神经传递中的作用，以及调节GABA能神经传递作为AD治疗的可能性。
Alzheimer’s disease (AD) is characterized pathologically by the deposition of β-amyloid peptides (Aβ) and the accumulation of neurofibrillary tangles (NFTs) composed of hyper-phosphorylated tau. Regardless of the pathological hallmarks, synaptic dysfunction is widely accepted as a causal event in AD. Of the two major types of synapses in the central nervous system (CNS): glutamatergic and GABAergic, which provide excitatory and inhibitory outputs respectively, abundant data implicate an impaired glutamatergic system during disease progression. However, emerging evidence supports the notion that disrupted default neuronal network underlies impaired memory, and that alterations of GABAergic circuits, either plays a primary role or as a compensatory response to excitotoxicity, may also contribute to AD by disrupting the overall network function. The goal of this review is to provide an overview of the involvement of Aβ, tau and apolipoprotein E4 (apoE4), the major genetic risk factor in late-onset AD (LOAD), in GABAergic neurotransmission and the potential of modulating the GABAergic function as AD therapy.