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微小RNA生物标志物作为神经退行性疾病的下一代诊断工具:综述

MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.

作者信息

Azam Hafiz Muhammad Husnain, Rößling Rosa Ilse, Geithe Christiane, Khan Muhammad Moman, Dinter Franziska, Hanack Katja, Prüß Harald, Husse Britta, Roggenbuck Dirk, Schierack Peter, Rödiger Stefan

机构信息

Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany.

German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.

出版信息

Front Mol Neurosci. 2024 May 31;17:1386735. doi: 10.3389/fnmol.2024.1386735. eCollection 2024.

Abstract

Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells-all indicative of disease progression-before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Huntington's disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies.

摘要

神经退行性疾病(NDs)的特征是大脑或脊髓中的神经元出现异常,这些神经元逐渐失去功能,最终导致细胞死亡。在检查受影响的组织时,病理变化显示突触丧失、蛋白质错误折叠以及免疫细胞激活,所有这些都表明在严重临床症状出现之前疾病在进展。NDs的早期检测对于可能使用可延缓疾病进展的靶向药物至关重要。鉴于其复杂的病理生理特征和多样的临床症状,迫切需要针对NDs的灵敏且有效的诊断方法。诸如微小RNA(miRNA)等生物标志物已被确定为检测这些疾病的潜在工具。我们探讨miRNA在NDs背景下的关键作用,重点关注阿尔茨海默病、帕金森病、多发性硬化症、亨廷顿病和肌萎缩侧索硬化症。该综述深入研究了衰老与NDs之间的复杂关系,强调了衰老大脑中的结构和功能改变及其对疾病发展的影响。它阐明了miRNA和RNA结合蛋白如何参与NDs的发病机制,并强调了研究它们在衰老过程中的表达和功能的重要性。重要的是,miRNA对翻译后修饰(PTM)有重大影响,不仅影响神经系统,还影响广泛的组织和细胞类型。已发现特定的miRNA靶向参与泛素化或去泛素化过程的蛋白质,这些过程在调节蛋白质功能和稳定性方面起着重要作用。我们讨论了miRNA、PTM和NDs之间的联系。此外,该综述讨论了miRNA作为疾病早期检测生物标志物的意义,为诊断策略提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a58/11177777/ababa269e33a/fnmol-17-1386735-g001.jpg

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