Targeting chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapeutic potential.

IF 6.9 1区 医学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Jin Wu, Wan Xu, Ying Su, Guang-Hui Wang, Jing-Jing Ma
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引用次数: 0

Abstract

The pathological hallmarks of various neurodegenerative diseases including Parkinson's disease and Alzheimer's disease prominently feature the accumulation of misfolded proteins and neuroinflammation. Chaperone-mediated autophagy (CMA) has emerged as a distinct autophagic process that coordinates the lysosomal degradation of specific proteins bearing the pentapeptide motif Lys-Phe-Glu-Arg-Gln (KFERQ), a recognition target for the cytosolic chaperone HSC70. Beyond its role in protein quality control, recent research underscores the intimate interplay between CMA and immune regulation in neurodegeneration. In this review, we illuminate the molecular mechanisms and regulatory pathways governing CMA. We further discuss the potential roles of CMA in maintaining neuronal proteostasis and modulating neuroinflammation mediated by glial cells. Finally, we summarize the recent advancements in CMA modulators, emphasizing the significance of activating CMA for the therapeutic intervention in neurodegenerative diseases.

针对神经退行性疾病中伴侣介导的自噬:机制和治疗潜力。
包括帕金森病和阿尔茨海默病在内的各种神经退行性疾病的病理特征突出表现为错误折叠蛋白的积累和神经炎症。伴侣介导的自噬(CMA)是一种独特的自噬过程,它协调溶酶体降解带有五肽图案 Lys-Phe-Glu-Arg-Gln (KFERQ) 的特定蛋白质,而 Lys-Phe-Glu-Arg-Gln 是细胞质伴侣 HSC70 的识别目标。除了在蛋白质质量控制中的作用外,最近的研究还强调了 CMA 与神经变性中免疫调节之间的密切相互作用。在这篇综述中,我们将阐明支配 CMA 的分子机制和调控途径。我们进一步讨论了 CMA 在维持神经元蛋白稳态和调节神经胶质细胞介导的神经炎症中的潜在作用。最后,我们总结了 CMA 调节剂的最新进展,强调了激活 CMA 对治疗干预神经退行性疾病的重要意义。
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来源期刊
Acta Pharmacologica Sinica
Acta Pharmacologica Sinica 医学-化学综合
CiteScore
15.10
自引率
2.40%
发文量
4365
审稿时长
2 months
期刊介绍: APS (Acta Pharmacologica Sinica) welcomes submissions from diverse areas of pharmacology and the life sciences. While we encourage contributions across a broad spectrum, topics of particular interest include, but are not limited to: anticancer pharmacology, cardiovascular and pulmonary pharmacology, clinical pharmacology, drug discovery, gastrointestinal and hepatic pharmacology, genitourinary, renal, and endocrine pharmacology, immunopharmacology and inflammation, molecular and cellular pharmacology, neuropharmacology, pharmaceutics, and pharmacokinetics. Join us in sharing your research and insights in pharmacology and the life sciences.
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