Cheng Xiaofang, Wu Jian, Geng Miao, Xiong Jiaxiang
Department of Physiology, Third Military Medical University, Chongqing, China.
Institute of Geriatrics, General Hospital of Chinese PLA, Beijing, China.
Neurobiol Aging. 2014 Jun;35(6):1217-32. doi: 10.1016/j.neurobiolaging.2013.11.021. Epub 2013 Nov 28.
Alzheimer's disease (AD) is the most common form of dementia. Accumulation of amyloid-beta (Aβ) peptides is regarded as the critical component associated with AD pathogenesis, which is derived from the amyloid precursor protein (APP) cleavage. Recent studies suggest that synaptic activity is one of the most important factors that regulate Aβ levels. It has been found that synaptic activity facilitates APP internalization and influences APP cleavage. Glutamatergic, cholinergic, serotonergic, leptin, adrenergic, orexin, and gamma-amino butyric acid receptors, as well as the activity-regulated cytoskeleton-associated protein (Arc) are all involved in these processes. The present review summarizes the evidence for synaptic activity-modulated Aβ levels and the mechanisms underlying this regulation. Interestingly, the immediate early gene product Arc may also be the downstream signaling molecule of several receptors in the synaptic activity-modulated Aβ levels. Elucidating how Aβ levels are regulated by synaptic activity may provide new insights in both the understanding of the pathogenesis of AD and in the development of therapies to slow down the progression of AD.
阿尔茨海默病（AD）是最常见的痴呆形式。β-淀粉样蛋白（Aβ）肽的积累被认为是与AD发病机制相关的关键因素，其来源于淀粉样前体蛋白（APP）的裂解。最近的研究表明，突触活动是调节Aβ水平的最重要因素之一。已经发现，突触活动促进APP内化并影响APP裂解。谷氨酸能、胆碱能、血清素能、瘦素、肾上腺素能、食欲素和γ-氨基丁酸受体，以及活性调节细胞骨架相关蛋白（Arc）都参与了这些过程。本综述总结了突触活动调节Aβ水平的证据以及这种调节的潜在机制。有趣的是，即刻早期基因产物Arc也可能是突触活动调节Aβ水平中几种受体的下游信号分子。阐明突触活动如何调节Aβ水平可能为理解AD的发病机制以及开发减缓AD进展的疗法提供新的见解。
