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自噬悖论:神经退行性疾病的新假说。

The autophagy paradox: A new hypothesis in neurodegenerative disorders.

机构信息

Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Basic Medical Sciences, Khoy University of Medical Sciences, Khoy, Iran; Student Research Committee, Khoy University of Medical Sciences, Khoy, Iran.

出版信息

Neurochem Int. 2024 Oct;179:105827. doi: 10.1016/j.neuint.2024.105827. Epub 2024 Aug 5.

Abstract

A recent study showed that while autophagy is usually tied to protein and organelle turnover, it can also play dual roles in neurodegenerative diseases. Traditionally, autophagy was seen as protective since it removes damaged proteins and organelles. but new data suggests autophagy can sometimes promote neuron death. and This review tackles autophagy's seemingly contradictory effects in neurodegeneration, or the "autophagy paradox. " It offers a framework for understanding autophagy in neurodegenerative research and the cellular processes involved. In short, our data uncovers a harmful autophagy role in certain situations, conflicting the view that it's always beneficial. We describe the distinct, disease-specific autophagy pathways functioning in various neurodegenerative diseases. Part two concerns potential therapeutic implications of manipulating autophagy and current strategies targeting the autophagic system, suggesting interesting areas for future research into tailored modulators. This could eventually enable activating or controlling specific autophagy pathways and aid in developing more effective treatments. Researchers believe more molecular-level research is needed so patient-tailored autophagy-modulating therapeutics can be developed given this dilemma. Moreover, research must translate faster into effective neurodegenerative disease treatment options. This article aims to provide a wholly new perspective on autophagy's classically described role in these severe diseases, challenging current dogma and opening new therapeutic avenue options.

摘要

最近的一项研究表明,虽然自噬通常与蛋白质和细胞器的周转有关,但它在神经退行性疾病中也可以发挥双重作用。传统上,自噬被认为是具有保护作用的,因为它可以清除受损的蛋白质和细胞器。但新的数据表明,自噬有时会促进神经元死亡。 本篇综述探讨了自噬在神经退行性变中的看似矛盾的作用,即“自噬悖论”。它为理解神经退行性研究中的自噬以及涉及的细胞过程提供了一个框架。简而言之,我们的数据揭示了自噬在某些情况下具有有害作用,这与自噬总是有益的观点相矛盾。我们描述了在各种神经退行性疾病中起作用的不同的、特定于疾病的自噬途径。第二部分涉及操纵自噬的潜在治疗意义以及针对自噬系统的当前策略,为未来针对特定调节剂的研究提供了有趣的领域。这最终可能使激活或控制特定的自噬途径并有助于开发更有效的治疗方法成为可能。研究人员认为,鉴于这一困境,需要进行更多的分子水平研究,以便开发针对患者的自噬调节剂治疗方法。此外,研究必须更快地转化为有效的神经退行性疾病治疗选择。本文旨在为自噬在这些严重疾病中经典描述的作用提供全新的视角,挑战当前的教条,开辟新的治疗途径。

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