线粒体和细胞生物能量学：越来越被认可的阿尔茨海默病的组成部分和可能的病因。
Mitochondria and cell bioenergetics: increasingly recognized components and a possible etiologic cause of Alzheimer's disease.
机构信息
Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA.
出版信息
Antioxid Redox Signal. 2012 Jun 15;16(12):1434-55. doi: 10.1089/ars.2011.4149. Epub 2011 Sep 15.
Abstract
SIGNIFICANCE
Mitochondria and brain bioenergetics are increasingly thought to play an important role in Alzheimer's disease (AD).
RECENT ADVANCES
Data that support this view are discussed from the perspective of the amyloid cascade hypothesis, which assumes beta-amyloid perturbs mitochondrial function, and from an opposite perspective that assumes mitochondrial dysfunction promotes brain amyloidosis. A detailed review of cytoplasmic hybrid (cybrid) studies, which argue mitochondrial DNA (mtDNA) contributes to sporadic AD, is provided. Recent AD endophenotype data that further suggest an mtDNA contribution are also summarized.
CRITICAL ISSUES AND FUTURE DIRECTIONS
Biochemical, molecular, cybrid, biomarker, and clinical data pertinent to the mitochondria-bioenergetics-AD nexus are synthesized and the mitochondrial cascade hypothesis, which represents a mitochondria-centric attempt to conceptualize sporadic AD, is discussed.
摘要
意义
线粒体和大脑生物能量学被认为在阿尔茨海默病（AD）中起着重要作用。
最新进展
从淀粉样蛋白级联假说的角度讨论了支持这一观点的数据，该假说假设β-淀粉样蛋白扰乱线粒体功能，以及从相反的角度假设线粒体功能障碍促进脑淀粉样变性。提供了对细胞质杂种（cybrid）研究的详细评论，这些研究认为线粒体 DNA（mtDNA）导致散发性 AD。还总结了最近的 AD 内表型数据，这些数据进一步表明 mtDNA 的作用。
关键问题和未来方向
综合了与线粒体-生物能-AD 联系有关的生化、分子、cybrid、生物标志物和临床数据，并讨论了线粒体级联假说，该假说代表了一种以线粒体为中心的概念化散发性 AD 的尝试。
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