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帕金森病中的微小RNA:从发病机制到诊疗方法

miRNA in Parkinson's disease: From pathogenesis to theranostic approaches.

作者信息

Elangovan Ajay, Venkatesan Dhivya, Selvaraj Priyanka, Pasha Md Younus, Babu Harysh Winster Suresh, Iyer Mahalaxmi, Narayanasamy Arul, Subramaniam Mohana Devi, Valsala Gopalakrishnan Abilash, Kumar Nachimuthu Senthil, Vellingiri Balachandar

机构信息

Department of Human Genetics and Molecular Biology, Human Molecular Cytogenetics and Stem Cell Laboratory, Bharathiar University, Tamil Nadu, Coimbatore, India.

Department of Zoology, Disease Proteomics Laboratory, Bharathiar University, Tamil Nadu, Coimbatore, India.

出版信息

J Cell Physiol. 2023 Feb;238(2):329-354. doi: 10.1002/jcp.30932. Epub 2022 Dec 11.

Abstract

Parkinson's disease (PD) is an age associated neurological disorder which is specified by cardinal motor symptoms such as tremor, stiffness, bradykinesia, postural instability, and non-motor symptoms. Dopaminergic neurons degradation in substantia nigra region and aggregation of αSyn are the classic signs of molecular defects noticed in PD pathogenesis. The discovery of microRNAs (miRNA) predicted to have a pivotal part in various processes regarding regularizing the cellular functions. Studies on dysregulation of miRNA in PD pathogenesis has recently gained the concern where our review unravels the role of miRNA expression in PD and its necessity in clinical validation for therapeutic development in PD. Here, we discussed how miRNA associated with ageing process in PD through molecular mechanistic approach of miRNAs on sirtuins, tumor necrosis factor-alpha and interleukin-6, dopamine loss, oxidative stress and autophagic dysregulation. Further we have also conferred the expression of miRNAs affected by SNCA gene expression, neuronal differentiation and its therapeutic potential with PD. In conclusion, we suggest more rigorous studies should be conducted on understanding the mechanisms and functions of miRNA in PD which will eventually lead to discovery of novel and promising therapeutics for PD.

摘要

帕金森病(PD)是一种与年龄相关的神经疾病,其特征为震颤、僵硬、运动迟缓、姿势不稳等主要运动症状以及非运动症状。黑质区域多巴胺能神经元的退化和α突触核蛋白的聚集是帕金森病发病机制中分子缺陷的典型迹象。微小RNA(miRNA)的发现预计在调节细胞功能的各种过程中起关键作用。最近,关于miRNA在帕金森病发病机制中失调的研究受到关注,我们的综述揭示了miRNA表达在帕金森病中的作用及其在帕金森病治疗开发临床验证中的必要性。在此,我们通过miRNA对沉默调节蛋白、肿瘤坏死因子-α和白细胞介素-6、多巴胺丧失、氧化应激和自噬失调的分子机制探讨了miRNA如何与帕金森病的衰老过程相关联。此外,我们还讨论了受α-突触核蛋白(SNCA)基因表达、神经元分化影响的miRNA的表达及其对帕金森病的治疗潜力。总之,我们建议应进行更严格的研究以了解miRNA在帕金森病中的机制和功能,这最终将导致发现针对帕金森病的新型且有前景的治疗方法。

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