Righes Giulio, Semenzato Luana, Koutsikos Konstantinos, Zanato Veronica, Pinton Paolo, Giorgi Carlotta, Patergnani Simone
Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies, University of Ferrara, Ferrara, Italy.
Department of Neurorehabilitation, IRCCS San Camillo Hospital, Venice, Italy.
Autophagy Rep. 2025 Jul 22;4(1):2529196. doi: 10.1080/27694127.2025.2529196. eCollection 2025.
Autophagy is a crucial cellular process responsible for the degradation and recycling of damaged or unnecessary components, maintaining cellular homeostasis and protecting against stress. Dysregulation of autophagy has been implicated in a variety of neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Various types of autophagy exist, each with distinct mechanisms, such as macroautophagy, mitophagy, lipophagy, and chaperone-mediated autophagy. These processes are essential for the removal of toxic substrates like protein aggregates and dysfunctional mitochondria, which are vital for neuronal health. In neurodegenerative diseases, the impairment of these clearance mechanisms leads to the accumulation of harmful substances, which accelerate disease progression. Modulating autophagy has emerged as a promising therapeutic strategy, with ongoing studies investigating molecules that can either stimulate or regulate this process. However, despite its potential, significant challenges remain in translating preclinical findings into clinically effective treatments. In this review, we will explore the different types of autophagy, their roles in neurodegenerative diseases, and the therapeutic potential associated with modulating these processes.
自噬是一种关键的细胞过程，负责降解和回收受损或不必要的成分，维持细胞内稳态并抵御应激。自噬失调与多种神经退行性疾病有关，包括多发性硬化症、阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿舞蹈症。存在多种类型的自噬，每种自噬都有独特的机制，如巨自噬、线粒体自噬、脂质自噬和伴侣介导的自噬。这些过程对于清除蛋白质聚集体和功能失调的线粒体等有毒底物至关重要，而这些底物对神经元健康至关重要。在神经退行性疾病中，这些清除机制的受损会导致有害物质的积累，从而加速疾病进展。调节自噬已成为一种有前景的治疗策略，目前有研究正在探索能够刺激或调节这一过程的分子。然而，尽管自噬具有潜力，但将临床前研究结果转化为临床有效治疗方法仍面临重大挑战。在这篇综述中，我们将探讨不同类型的自噬、它们在神经退行性疾病中的作用以及与调节这些过程相关的治疗潜力。
