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神经退行性疾病和衰老中的自噬。

Mitophagy in neurodegeneration and aging.

机构信息

Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA; Danish Aging Research Center, Department of Molecular Biology and Genetics, University of Aarhus, 8000 Aarhus C, Denmark.

出版信息

Neurochem Int. 2017 Oct;109:202-209. doi: 10.1016/j.neuint.2017.02.007. Epub 2017 Feb 21.

Abstract

Mitochondrial dysfunction contributes to normal aging and a wide spectrum of age-related diseases, including neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. It is important to maintain a healthy mitochondrial population which is tightly regulated by proteolysis and mitophagy. Mitophagy is a specialized form of autophagy that regulates the turnover of damaged and dysfunctional mitochondria, organelles that function in producing energy for the cell in the form of ATP and regulating energy homeostasis. Mechanistic studies on mitophagy across species highlight a sophisticated and integrated cellular network that regulates the degradation of mitochondria. Strategies directed at maintaining a healthy mitophagy level in aged individuals might have beneficial effects. In this review, we provide an updated mechanistic overview of mitophagy pathways and discuss the role of reduced mitophagy in neurodegeneration. We also highlight potential translational applications of mitophagy-inducing compounds, such as NAD precursors and urolithins.

摘要

线粒体功能障碍与正常衰老以及广泛的与年龄相关的疾病有关,包括神经退行性疾病,如帕金森病和阿尔茨海默病。保持健康的线粒体群体非常重要,线粒体群体受到蛋白质水解和线粒体自噬的严格调节。线粒体自噬是一种特殊的自噬形式,可调节受损和功能失调的线粒体的周转率,这些细胞器以 ATP 的形式为细胞产生能量,并调节能量稳态。跨物种的线粒体自噬的机制研究强调了一个复杂而综合的细胞网络,该网络调节线粒体的降解。针对维持衰老个体健康的线粒体自噬水平的策略可能具有有益的效果。在这篇综述中,我们提供了线粒体自噬途径的最新机制概述,并讨论了减少的线粒体自噬在神经退行性变中的作用。我们还强调了线粒体自噬诱导化合物(如 NAD 前体和尿石素)的潜在转化应用。

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