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阿尔茨海默病中选择性自噬亚型的机制性见解

Mechanistic Insights into Selective Autophagy Subtypes in Alzheimer's Disease.

作者信息

Guan Xinjie, Iyaswamy Ashok, Sreenivasmurthy Sravan Gopalkrishnashetty, Su Chengfu, Zhu Zhou, Liu Jia, Kan Yuxuan, Cheung King-Ho, Lu Jiahong, Tan Jieqiong, Li Min

机构信息

Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.

Institute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen 518057, China.

出版信息

Int J Mol Sci. 2022 Mar 25;23(7):3609. doi: 10.3390/ijms23073609.

Abstract

Eukaryotic cells possess a plethora of regulatory mechanisms to maintain homeostasis and ensure proper biochemical functionality. Autophagy, a central, conserved self-consuming process of the cell, ensures the timely degradation of damaged cellular components. Several studies have demonstrated the important roles of autophagy activation in mitigating neurodegenerative diseases, especially Alzheimer's disease (AD). However, surprisingly, activation of macroautophagy has not shown clinical efficacy. Hence, alternative strategies are urgently needed for AD therapy. In recent years, selective autophagy has been reported to be involved in AD pathology, and different subtypes have been identified, such as aggrephagy, mitophagy, reticulophagy, lipophagy, pexophagy, nucleophagy, lysophagy and ribophagy. By clarifying the underlying mechanisms governing these various subtypes, we may come to understand how to control autophagy to treat AD. In this review, we summarize the latest findings concerning the role of selective autophagy in the pathogenesis of AD. The evidence overwhelmingly suggests that selective autophagy is an active mechanism in AD pathology, and that regulating selective autophagy would be an effective strategy for controlling this pathogenesis.

摘要

真核细胞拥有大量的调节机制来维持体内平衡并确保适当的生化功能。自噬是细胞的一个核心、保守的自我消耗过程,可确保受损细胞成分的及时降解。多项研究表明自噬激活在减轻神经退行性疾病,尤其是阿尔茨海默病(AD)方面具有重要作用。然而,令人惊讶的是,巨自噬的激活尚未显示出临床疗效。因此,AD治疗迫切需要替代策略。近年来,有报道称选择性自噬参与AD病理过程,并且已经鉴定出不同的亚型,如聚集体自噬、线粒体自噬、内质网自噬、脂自噬、过氧化物酶体自噬、核自噬、溶酶体自噬和核糖体自噬。通过阐明控制这些不同亚型的潜在机制,我们可能会明白如何控制自噬来治疗AD。在这篇综述中,我们总结了关于选择性自噬在AD发病机制中作用的最新发现。证据压倒性地表明,选择性自噬是AD病理过程中的一种活跃机制,调节选择性自噬将是控制这种发病机制的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37d3/8998506/de3d8b65ba83/ijms-23-03609-g001.jpg

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