2025/03/13 by Rajesh Tamatta, Abhishek Kumar Singh · 2 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #MicroRNA in disease regulation #Autophagy in Disease and Therapy #Circular RNAs in diseases
paper · doi:10.1016/j.lfs.2025.123563
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. • During brain aging, the miRNA profile significantly changes, one of the risk factors for developing age-related neurodegenerative disorders (NDDs). • Targeting miRNAs regulating autophagy and proteostasis provides therapeutic potential for age-related NDDs. • Modulating miRNAs that influence autophagy and proteostasis offers therapeutic potential to delay aging and NDDs. • miRNA profiles, autophagy markers, and proteostasis regulators are key biomarkers for aging and age-related diseases, enabling early diagnosis and intervention.