Critical role of microRNAs in cellular quality control during brain aging and neurological disorders: Interplay between autophagy and proteostasis

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-03-13 DOI:10.1016/j.lfs.2025.123563

Rajesh Tamatta, Abhishek Kumar Singh

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Abstract

A decline in cellular quality control mechanisms is one of the processes of brain aging. Autophagy and proteostasis are two regulatory mechanisms that maintain cellular component turnover to preserve cellular homeostasis, optimal function, and neuronal health by eliminating damaged and aggregated proteins and preventing neurodegenerative disorders (NDDs). Impaired autophagy and proteostasis are significant hallmarks of aging and many age-related NDDs. MicroRNAs are noncoding RNA molecules that have recently been shown to be essential for regulating several biological processes, such as autophagy, proteostasis, cellular differentiation, and development by targeting mRNA's 3’untranslated region (3’UTR). During brain aging, miRNAs have been shown to dysregulate proteostasis and autophagy, resulting in abnormal cellular activity and protein aggregation, a characteristic of age-related NDDs. This review highlights the complex interactions of miRNAs in the orchestration of proteostasis and autophagy. This dysregulation impairs autophagic flux and proteostasis and accelerates age-related disorders, neuroinflammation, and neurodegeneration. Understanding the complex interactions among miRNAs, autophagy, and proteostasis in the aging brain is essential for novel therapeutics development for age-related NDDs.

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在脑老化和神经系统疾病过程中，microrna在细胞质量控制中的关键作用：自噬和蛋白质平衡之间的相互作用

细胞质量控制机制的下降是大脑衰老的过程之一。自噬和蛋白质平衡是两种维持细胞成分更新的调节机制，通过消除受损和聚集的蛋白质和预防神经退行性疾病（ndd）来保持细胞稳态、最佳功能和神经元健康。自噬和蛋白平衡受损是衰老和许多与年龄相关的ndd的显著标志。microrna是一种非编码RNA分子，最近被证明在调节一些生物过程中是必不可少的，如自噬、蛋白酶抑制、细胞分化和通过靶向mRNA的3 ‘非翻译区（3’UTR）进行发育。在大脑衰老过程中，miRNAs被证明会失调蛋白质稳态和自噬，导致细胞活性和蛋白质聚集异常，这是与年龄相关的ndd的一个特征。这篇综述强调了mirna在蛋白质静止和自噬协调中的复杂相互作用。这种失调损害了自噬通量和蛋白质平衡，加速了与年龄相关的疾病、神经炎症和神经变性。了解衰老大脑中mirna、自噬和蛋白质平衡之间的复杂相互作用对于开发与年龄相关的ndd的新疗法至关重要。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.