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衰老与神经退行性变中的星形胶质细胞蛋白质稳态

Astrocytic proteostasis in the tale of aging and neurodegeneration.

作者信息

Cabral-Miranda Felipe, Matias Isadora, Gomes Flávia Carvalho Alcantara

机构信息

Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Ageing Res Rev. 2025 Jan;103:102580. doi: 10.1016/j.arr.2024.102580. Epub 2024 Nov 16.

Abstract

Homeostasis of proteins (proteostasis), which governs protein processing, folding, quality control, and degradation, is a fundamental cellular process that plays a pivotal role in various neurodegenerative diseases and in the natural aging process of the mammalian brain. While the role of neuronal proteostasis in neuronal physiology is well characterized, the contribution of proteostasis of glial cells, particularly of astrocytes, has received fairly less attention in this context. Here, we summarize recent data highlighting proteostasis dysfunction in astrocytes and its putative implication to neurodegenerative diseases and aging. We discuss how distinct proteostasis nodes and pathways in astrocytes may specifically contribute to brain function and different age-associated pathologies. Finally, we argue that the understanding of astrocytic proteostasis role in neuronal physiology and functional decay may arise as a potential new avenue of intervention in neurodegenerative diseases and grant relevant data in the biology of aging.

摘要

蛋白质稳态(蛋白稳态)调控着蛋白质的加工、折叠、质量控制和降解,是一种基本的细胞过程,在各种神经退行性疾病以及哺乳动物大脑的自然衰老过程中起着关键作用。虽然神经元蛋白稳态在神经元生理学中的作用已得到充分表征,但在这种情况下,神经胶质细胞尤其是星形胶质细胞的蛋白稳态的贡献受到的关注相对较少。在这里,我们总结了最近的数据,这些数据突出了星形胶质细胞中蛋白稳态功能障碍及其对神经退行性疾病和衰老的潜在影响。我们讨论了星形胶质细胞中不同的蛋白稳态节点和途径如何可能具体地促进脑功能和不同的年龄相关病理。最后,我们认为,对星形胶质细胞蛋白稳态在神经元生理学和功能衰退中的作用的理解,可能会成为神经退行性疾病干预的一个潜在新途径,并为衰老生物学提供相关数据。

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