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靶向阿尔茨海默病中的线粒体自噬

Targeting Mitophagy in Alzheimer's Disease.

作者信息

Jayatunga Dona P W, Hone Eugene, Bharadwaj Prashant, Garg Manohar, Verdile Giuseppe, Guillemin Gilles J, Martins Ralph N

机构信息

Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.

Cooperative Research Centre for Mental Health, Carlton, VIC, Australia.

出版信息

J Alzheimers Dis. 2020;78(4):1273-1297. doi: 10.3233/JAD-191258.

Abstract

Mitochondria perform many essential cellular functions including energy production, calcium homeostasis, transduction of metabolic and stress signals, and mediating cell survival and death. Maintaining viable populations of mitochondria is therefore critical for normal cell function. The selective disposal of damaged mitochondria, by a pathway known as mitophagy, plays a key role in preserving mitochondrial integrity and quality. Mitophagy reduces the formation of reactive oxygen species and is considered as a protective cellular process. Mitochondrial dysfunction and deficits of mitophagy have important roles in aging and especially in neurodegenerative disorders such as Alzheimer's disease (AD). Targeting mitophagy pathways has been suggested to have potential therapeutic effects against AD. In this review, we aim to briefly discuss the emerging concepts on mitophagy, molecular regulation of the mitophagy process, current mitophagy detection methods, and mitophagy dysfunction in AD. Finally, we will also briefly examine the stimulation of mitophagy as an approach for attenuating neurodegeneration in AD.

摘要

线粒体执行许多基本的细胞功能,包括能量产生、钙稳态、代谢和应激信号转导,以及介导细胞存活和死亡。因此,维持线粒体的存活群体对于正常细胞功能至关重要。通过一种称为线粒体自噬的途径选择性清除受损线粒体,在维持线粒体完整性和质量方面起着关键作用。线粒体自噬减少活性氧的形成,被认为是一种保护性的细胞过程。线粒体功能障碍和线粒体自噬缺陷在衰老过程中,尤其是在神经退行性疾病如阿尔茨海默病(AD)中起重要作用。针对线粒体自噬途径已被认为对AD具有潜在的治疗作用。在这篇综述中,我们旨在简要讨论线粒体自噬的新兴概念、线粒体自噬过程的分子调控、当前线粒体自噬检测方法以及AD中的线粒体自噬功能障碍。最后,我们还将简要探讨刺激线粒体自噬作为减轻AD神经退行性变的一种方法。

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