The autophagy paradox: A new hypothesis in neurodegenerative disorders

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-08-05 DOI:10.1016/j.neuint.2024.105827
Haleh Barmaki , Alireza Nourazarian , Behrouz Shademan , Fatemeh khaki-khatibi
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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.

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自噬悖论:神经退行性疾病的新假说。
最近的一项研究表明,虽然自噬通常与蛋白质和细胞器的更替有关,但它在神经退行性疾病中也能发挥双重作用。本综述探讨了自噬在神经退行性疾病中看似矛盾的作用,即 "自噬悖论"。"它为理解神经退行性病变研究中的自噬及其所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的有害作用,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发挥作用的不同的、针对特定疾病的自噬途径。第二部分涉及操纵自噬的潜在治疗意义和当前针对自噬系统的策略,并提出了未来研究定制调节剂的有趣领域。这最终可以激活或控制特定的自噬途径,帮助开发更有效的治疗方法。研究人员认为,鉴于这种困境,需要开展更多分子水平的研究,以便开发出适合患者的自噬调节疗法。此外,研究必须更快地转化为有效的神经退行性疾病治疗方案。本文旨在从一个全新的视角探讨自噬在这些严重疾病中的经典作用,挑战当前的教条,开辟新的治疗途径选择。
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来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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