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帕金森病患者脑脊液中微小RNA和蛋白质的生物学功能分析

Biological Function Analysis of MicroRNAs and Proteins in the Cerebrospinal Fluid of Patients with Parkinson's Disease.

作者信息

Hwang Ji Su, Kim Seok Gi, George Nimisha Pradeep, Kwon Minjun, Jang Yong Eun, Lee Sang Seop, Lee Gwang

机构信息

Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.

Department of Physiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Dec 10;25(24):13260. doi: 10.3390/ijms252413260.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by alpha-synuclein aggregation into Lewy bodies in the neurons. Cerebrospinal fluid (CSF) is considered the most suited source for investigating PD pathogenesis and identifying biomarkers. While microRNA (miRNA) profiling can aid in the investigation of post-transcriptional regulation in neurodegenerative diseases, information on miRNAs in the CSF of patients with PD remains limited. This review combines miRNA analysis with proteomic profiling to explore the collective impact of CSF miRNAs on the neurodegenerative mechanisms in PD. We constructed separate networks for altered miRNAs and proteomes using a bioinformatics method. Altered miRNAs were poorly linked to biological functions owing to limited information; however, changes in protein expression were strongly associated with biological functions. Subsequently, the networks were integrated for further analysis. In silico prediction from the integrated network revealed relationships between miRNAs and proteins, highlighting increased reactive oxygen species generation, neuronal loss, and neurodegeneration and suppressed ATP synthesis, mitochondrial function, and neurotransmitter release in PD. The approach suggests the potential of miRNAs as biomarkers for critical mechanisms underlying PD. The combined strategy could enhance our understanding of the complex biochemical networks of miRNAs in PD and support the development of diagnostic and therapeutic strategies for precision medicine.

摘要

帕金森病(PD)是一种进行性神经退行性疾病,其特征是α-突触核蛋白在神经元中聚集成路易小体。脑脊液(CSF)被认为是研究PD发病机制和鉴定生物标志物的最适宜来源。虽然微小RNA(miRNA)谱分析有助于研究神经退行性疾病中的转录后调控,但关于PD患者脑脊液中miRNA的信息仍然有限。本综述将miRNA分析与蛋白质组学分析相结合,以探讨脑脊液miRNA对PD神经退行性机制的综合影响。我们使用生物信息学方法构建了miRNA和蛋白质组改变的独立网络。由于信息有限,改变的miRNA与生物学功能的联系较弱;然而,蛋白质表达的变化与生物学功能密切相关。随后,将这些网络整合以进行进一步分析。综合网络的计算机预测揭示了miRNA与蛋白质之间的关系,突出了PD中活性氧生成增加、神经元丢失和神经退行性变,以及ATP合成、线粒体功能和神经递质释放受到抑制。该方法表明miRNA作为PD潜在关键机制生物标志物的可能性。这种联合策略可以增强我们对PD中miRNA复杂生化网络的理解,并支持精准医学诊断和治疗策略的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b27/11678473/5f1354d09638/ijms-25-13260-g001.jpg

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