Mitochondrial Aspects of Synaptic Dysfunction in Alzheimer's Disease.
Mitochondrial Aspects of Synaptic Dysfunction in Alzheimer's Disease.
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DOI：
10.3233/jad-160726
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Tammineni P
中科院分区：
文献类型：
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作者：
Cai Q;Tammineni P
阿尔茨海默病(AD)的特征是大脑中淀粉样斑块和tau神经原纤维缠结的沉积，并伴随着认知能力的稳步下降。突触损伤是一种早期的病理事件，与认知缺陷和记忆丧失密切相关。线粒体是突触功能的重要细胞器。神经元利用特殊的机制驱动线粒体运输到突触，在突触中线粒体缓冲钙离子，并通过提供ATP来维持神经递质的释放，作为局部能量来源。线粒体异常是阿尔茨海默病患者脑内最早和最显著的特征之一。淀粉样蛋白-β(A-β)和tau都会引发线粒体改变。越来越多的证据表明，线粒体的扰动是阿尔茨海默病突触失败和变性的关键因素。线粒体在支持突触功能中的重要性使其成为AD新的治疗策略的靶点。在这里，我们回顾了调控突触线粒体功能的分子机制，重点介绍了最近关于AD患者线粒体动力学和运输障碍的研究结果，并讨论了这些变化如何影响突触小泡的释放，从而促进与AD相关的突触病理。
Alzheimer’s disease (AD) is characterized by brain deposition of amyloid plaques and tau neurofibrillary tangles along with steady cognitive decline. Synaptic damage, an early pathological event, correlates strongly with cognitive deficits and memory loss. Mitochondria are essential organelles for synaptic function. Neurons utilize specialized mechanisms to drive mitochondrial trafficking to synapses in which mitochondria buffer Ca2+ and serve as local energy sources by supplying ATP to sustain neurotransmitter release. Mitochondrial abnormalities are one of the earliest and prominent features in AD patient brains. Amyloid-β (Aβ) and tau both trigger mitochondrial alterations. Accumulating evidence suggests that mitochondrial perturbation acts as a key factor that is involved in synaptic failure and degeneration in AD. The importance of mitochondria in supporting synaptic function has made them a promising target of new therapeutic strategy for AD. Here, we review the molecular mechanisms regulating mitochondrial function at synapses, highlight recent findings on the disturbance of mitochondrial dynamics and transport in AD, and discuss how these alterations impact synaptic vesicle release and thus contribute to synaptic pathology associated with AD.