β-淀粉样蛋白、线粒体功能障碍与突触损伤：对衰老及阿尔茨海默病认知衰退的影响
Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease.
作者信息
Reddy P Hemachandra, Beal M Flint
机构信息
Neurogenetics Laboratory, Neurological Sciences Institute, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
出版信息
Trends Mol Med. 2008 Feb;14(2):45-53. doi: 10.1016/j.molmed.2007.12.002. Epub 2008 Jan 22.
Abstract
Recent studies of postmortem brains from Alzheimer's disease (AD) patients and transgenic mouse models of AD suggest that oxidative damage, induced by amyloid beta (Abeta), is associated with mitochondria early in AD progression. Abeta and amyloid-precursor protein are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron-transport chain, increase reactive oxygen species production, cause mitochondrial damage and prevent neurons from functioning normally. Furthermore, accumulation of Abeta at synaptic terminals might contribute to synaptic damage and cognitive decline in patients with AD. Here, we describe recent studies regarding the roles of Abeta and mitochondrial function in AD progression and particularly in synaptic damage and cognitive decline.
摘要
最近对阿尔茨海默病（AD）患者的尸检大脑以及AD转基因小鼠模型的研究表明，在AD进展的早期，由β淀粉样蛋白（Aβ）诱导的氧化损伤与线粒体有关。已知Aβ和淀粉样前体蛋白定位于线粒体膜，阻断核编码的线粒体蛋白向线粒体的转运，与线粒体蛋白相互作用，破坏电子传递链，增加活性氧的产生，导致线粒体损伤并阻止神经元正常运作。此外，Aβ在突触末端的积累可能导致AD患者的突触损伤和认知能力下降。在此，我们描述了关于Aβ和线粒体功能在AD进展中，特别是在突触损伤和认知能力下降中的作用的近期研究。
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