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调控自噬的微小RNA:治疗神经退行性疾病的机遇

MicroRNAs regulating autophagy: opportunities in treating neurodegenerative diseases.

作者信息

Mohseni Mahdi, Behzad Ghazal, Farhadi Arezoo, Behroozi Javad, Mohseni Hamraz, Valipour Behnaz

机构信息

School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Front Neurosci. 2024 Nov 8;18:1397106. doi: 10.3389/fnins.2024.1397106. eCollection 2024.

Abstract

Neurodegenerative diseases (NDs) are increasingly prevalent in our aging population, imposing significant social and economic burdens. Currently, most ND patients receive only symptomatic treatment due to limited understanding of their underlying causes. Consequently, there is a pressing need for comprehensive research into the pathological mechanisms of NDs by both researchers and clinicians. Autophagy, a cellular mechanism responsible for maintaining cellular equilibrium by removing dysfunctional organelles and misfolded proteins, plays a vital role in cell health and is implicated in various diseases. MicroRNAs (miRNAs) exert influence on autophagy and hold promise for treating these diseases. These small oligonucleotides bind to the 3'-untranslated region (UTR) of target mRNAs, leading to mRNA silencing, degradation, or translation blockade. This review explores recent findings on the regulation of autophagy and autophagy-related genes by different miRNAs in various pathological conditions, including neurodegeneration and inflammation-related diseases. The recognition of miRNAs as key regulators of autophagy in human diseases has spurred investigations into pharmacological compounds and traditional medicines targeting these miRNAs in disease models. This has catalyzed a new wave of therapeutic interventions aimed at modulating autophagy.

摘要

神经退行性疾病(NDs)在老龄化人口中日益普遍,带来了巨大的社会和经济负担。目前,由于对其潜在病因了解有限,大多数ND患者仅接受对症治疗。因此,研究人员和临床医生迫切需要对NDs的病理机制进行全面研究。自噬是一种通过清除功能失调的细胞器和错误折叠的蛋白质来维持细胞平衡的细胞机制,在细胞健康中起着至关重要的作用,并与多种疾病有关。微小RNA(miRNAs)对自噬产生影响,有望用于治疗这些疾病。这些小寡核苷酸与靶mRNA的3'-非翻译区(UTR)结合,导致mRNA沉默、降解或翻译阻断。本综述探讨了在各种病理条件下,包括神经退行性变和炎症相关疾病,不同miRNAs对自噬及自噬相关基因调控的最新研究结果。将miRNAs视为人类疾病中自噬的关键调节因子,这激发了在疾病模型中针对这些miRNAs的药理化合物和传统药物的研究。这催生了一波旨在调节自噬的新的治疗干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37eb/11582054/00145bdb2b88/fnins-18-1397106-g001.jpg

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