自噬与神经保护。

Mitophagy and Neuroprotection.

机构信息

Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway.

Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Crete, Greece; Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, 70013, Crete, Greece.

出版信息

Trends Mol Med. 2020 Jan;26(1):8-20. doi: 10.1016/j.molmed.2019.07.002. Epub 2019 Jul 30.

DOI:10.1016/j.molmed.2019.07.002

PMID:31375365

Abstract

Neurodegenerative diseases are strongly age-related and currently cannot be cured, with a surge of patient numbers in the coming decades in view of the emerging worldwide ageing population, bringing healthcare and socioeconomic challenges. Effective therapies are urgently needed, and are dependent on new aetiological mechanisms. In neurons, efficient clearance of damaged mitochondria, through the highly evolutionary conserved cellular process termed mitophagy, plays a fundamental role in mitochondrial and metabolic homeostasis, energy supply, neuronal survival, and health. Conversely, defective mitophagy leads to accumulation of damaged mitochondria and cellular dysfunction, contributing to ageing and age-predisposed neurodegeneration. Here, we discuss the contribution of defective mitophagy in these diseases, and underlying molecular mechanisms, and highlight novel therapeutics based on new discovered mitophagy-inducing strategies.

摘要

神经退行性疾病与年龄密切相关，目前无法治愈。由于全球人口老龄化的出现，未来几十年患者数量将会激增，这给医疗保健和社会经济带来了挑战。因此，迫切需要有效的治疗方法，而这些方法又依赖于新的病因机制。在神经元中，通过高度进化保守的细胞过程自噬（mitophagy）来有效清除受损的线粒体，对于线粒体和代谢稳态、能量供应、神经元存活和健康都起着至关重要的作用。相反，自噬缺陷会导致受损线粒体的积累和细胞功能障碍，从而导致衰老和年龄易患的神经退行性变。在这里，我们讨论了自噬缺陷在这些疾病中的作用及其潜在的分子机制，并强调了基于新发现的诱导自噬策略的新型治疗方法。