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微小RNA介导的自噬通量调控:神经退行性疾病的新调控途径,重点关注朊病毒疾病

Regulation of MicroRNAs-Mediated Autophagic Flux: A New Regulatory Avenue for Neurodegenerative Diseases With Focus on Prion Diseases.

作者信息

Shah Syed Zahid Ali, Zhao Deming, Hussain Tariq, Sabir Naveed, Yang Lifeng

机构信息

National Animal Transmissible Spongiform Encephalopathy Laboratory and Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.

出版信息

Front Aging Neurosci. 2018 May 15;10:139. doi: 10.3389/fnagi.2018.00139. eCollection 2018.

Abstract

Prion diseases are fatal neurological disorders affecting various mammalian species including humans. Lack of proper diagnostic tools and non-availability of therapeutic remedies are hindering the control strategies for prion diseases. MicroRNAs (miRNAs) are abundant endogenous short non-coding essential RNA molecules that negatively regulate the target genes after transcription. Several biological processes depend on miRNAs, and altered profiles of these miRNAs are potential biomarkers for various neurodegenerative diseases, including prion diseases. Autophagic flux degrades the misfolded prion proteins to reduce chronic endoplasmic reticulum stress and enhance cell survival. Recent evidence suggests that specific miRNAs target and regulate the autophagic mechanism, which is critical for alleviating cellular stress. miRNAs-mediated regulation of these specific proteins involved in the autophagy represents a new target with highly significant therapeutic prospects. Here, we will briefly describe the biology of miRNAs, the use of miRNAs as potential biomarkers with their credibility, the regulatory mechanism of miRNAs in major neurodegenerative diseases such as Alzheimer's, Parkinson's, and prion diseases, degradation pathways for aggregated prion proteins, the role of autophagy in prion diseases. Finally, we will discuss the miRNAs-modulated autophagic flux in neurodegenerative diseases and employ them as potential therapeutic intervention strategy in prion diseases.

摘要

朊病毒疾病是影响包括人类在内的各种哺乳动物物种的致命性神经疾病。缺乏合适的诊断工具以及治疗方法的不可用,正在阻碍朊病毒疾病的控制策略。微小RNA(miRNA)是丰富的内源性短非编码必需RNA分子,在转录后对靶基因进行负调控。几个生物学过程依赖于miRNA,这些miRNA的改变谱是包括朊病毒疾病在内的各种神经退行性疾病的潜在生物标志物。自噬通量降解错误折叠的朊病毒蛋白,以减少慢性内质网应激并提高细胞存活率。最近的证据表明,特定的miRNA靶向并调节自噬机制,这对于减轻细胞应激至关重要。miRNA介导的对自噬中涉及的这些特定蛋白质的调节代表了一个具有高度显著治疗前景的新靶点。在这里,我们将简要描述miRNA的生物学特性、miRNA作为潜在生物标志物的用途及其可信度、miRNA在阿尔茨海默病、帕金森病和朊病毒疾病等主要神经退行性疾病中的调节机制、聚集的朊病毒蛋白的降解途径、自噬在朊病毒疾病中的作用。最后,我们将讨论神经退行性疾病中miRNA调节的自噬通量,并将它们用作朊病毒疾病的潜在治疗干预策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3573/5962651/3cd2230da24a/fnagi-10-00139-g001.jpg

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