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浅析 microRNAs 的生物发生和功能及其在帕金森病神经发病机制中的作用。

A Glance at Biogenesis and Functionality of MicroRNAs and Their Role in the Neuropathogenesis of Parkinson's Disease.

机构信息

Nicolaus Copernicus University in Toruń Ludwik Rydygier Collegium Medicum in Bydgoszcz, Faculty of Health Sciences, Department of Geriatrics, Bydgoszcz, Poland.

出版信息

Oxid Med Cell Longev. 2023 Jun 8;2023:7759053. doi: 10.1155/2023/7759053. eCollection 2023.

Abstract

MicroRNAs (miRNAs) are short, noncoding RNA transcripts. Mammalian miRNA coding sequences are located in introns and exons of genes encoding various proteins. As the central nervous system is the largest source of miRNA transcripts in living organisms, miRNA molecules are an integral part of the regulation of epigenetic activity in physiological and pathological processes. Their activity depends on many proteins that act as processors, transporters, and chaperones. Many variants of Parkinson's disease have been directly linked to specific gene mutations which in pathological conditions are cumulated resulting in the progression of neurogenerative changes. These mutations can often coexist with specific miRNA dysregulation. Dysregulation of different extracellular miRNAs has been confirmed in many studies on the PD patients. It seems reasonable to conduct further research on the role of miRNAs in the pathogenesis of Parkinson's disease and their potential use in future therapies and diagnosis of the disease. This review presents the current state of knowledge about the biogenesis and functionality of miRNAs in the human genome and their role in the neuropathogenesis of Parkinson's disease (PD)-one of the most common neurodegenerative disorders. The article also describes the process of miRNA formation which can occur in two ways-the canonical and noncanonical one. However, the main focus was on miRNA's use in in vitro and in vivo studies in the context of pathophysiology, diagnosis, and treatment of PD. Some issues, especially those regarding the usefulness of miRNAs in PD's diagnostics and especially its treatment, require further research. More standardization efforts and clinical trials on miRNAs are needed.

摘要

微小 RNA(miRNA)是短的非编码 RNA 转录物。哺乳动物 miRNA 编码序列位于编码各种蛋白质的基因的内含子和外显子中。由于中枢神经系统是生物体中 miRNA 转录本的最大来源,miRNA 分子是生理和病理过程中表观遗传活性调节的组成部分。它们的活性取决于许多充当处理器、转运体和伴侣的蛋白质。许多帕金森病的变体已直接与特定基因突变相关联,在病理条件下,这些基因突变会累积,导致神经退行性变化的进展。这些突变通常可以与特定的 miRNA 失调共存。在对 PD 患者的许多研究中已经证实了不同细胞外 miRNA 的失调。进一步研究 miRNA 在帕金森病发病机制中的作用及其在未来治疗和诊断该病中的潜在用途似乎是合理的。

这篇综述介绍了目前关于人类基因组中 miRNA 的生物发生和功能及其在帕金森病(PD)神经发病机制中的作用的知识状况,PD 是最常见的神经退行性疾病之一。文章还描述了 miRNA 形成的过程,它可以通过两种方式发生——经典和非经典方式。然而,主要重点是 miRNA 在 PD 病理生理学、诊断和治疗的体外和体内研究中的用途。

一些问题,特别是关于 miRNA 在 PD 诊断中的有用性,尤其是其治疗,需要进一步研究。需要更多关于 miRNA 的标准化努力和临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fcc/10270766/2713ef3bc134/OMCL2023-7759053.001.jpg

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