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帕金森病与 microRNAs:神经元细胞凋亡的抑制与刺激之博弈。

Parkinson's Disease and MicroRNAs: A Duel Between Inhibition and Stimulation of Apoptosis in Neuronal Cells.

机构信息

Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan.

Department of Pharmacy, Al-Noor University College, Nineveh, Iraq.

出版信息

Mol Neurobiol. 2024 Nov;61(11):8552-8574. doi: 10.1007/s12035-024-04111-w. Epub 2024 Mar 23.

Abstract

Parkinson's disease (PD) is one of the most prevalent diseases of central nervous system that is caused by degeneration of the substantia nigra's dopamine-producing neurons through apoptosis. Apoptosis is regulated by initiators' and executioners' caspases both in intrinsic and extrinsic pathways, further resulting in neuronal damage. In that context, targeting apoptosis appears as a promising therapeutic approach for treating neurodegenerative diseases. Non-coding RNAs-more especially, microRNAs, or miRNAs-are a promising target for the therapy of neurodegenerative diseases because they are essential for a number of cellular processes, including signaling, apoptosis, cell proliferation, and gene regulation. It is estimated that a substantial portion of coding genes (more than 60%) are regulated by miRNAs. These small regulatory molecules can have wide-reaching consequences on cellular processes like apoptosis, both in terms of intrinsic and extrinsic pathways. Furthermore, it was recommended that a disruption in miRNA expression levels could also result in perturbation of typical apoptosis pathways, which may be a factor in certain diseases like PD. The latest research on miRNAs and their impact on neural cell injury in PD models by regulating the apoptosis pathway is summarized in this review article. Furthermore, the importance of lncRNA/circRNA-miRNA-mRNA network for regulating apoptosis pathways in PD models and treatment is explored. These results can be utilized for developing new strategies in PD treatment.

摘要

帕金森病(PD)是最常见的中枢神经系统疾病之一,其病因是通过细胞凋亡导致黑质多巴胺能神经元的退化。凋亡受内在和外在途径中的起始和执行 caspase 的调节,进一步导致神经元损伤。在这种情况下,靶向细胞凋亡似乎是治疗神经退行性疾病的一种有前途的治疗方法。非编码 RNA——尤其是 microRNA(miRNA)——是神经退行性疾病治疗的一个有前途的靶点,因为它们对许多细胞过程至关重要,包括信号转导、细胞凋亡、细胞增殖和基因调控。据估计,大部分编码基因(超过 60%)受 miRNA 调控。这些小的调节分子可以对细胞凋亡等内在和外在途径中的细胞过程产生广泛的影响。此外,还建议 miRNA 表达水平的紊乱也可能导致典型凋亡途径的紊乱,这可能是 PD 等某些疾病的一个因素。本文综述了 miRNA 及其通过调节细胞凋亡途径对 PD 模型中神经细胞损伤的最新研究,探讨了 lncRNA/circRNA-miRNA-mRNA 网络在调控 PD 模型和治疗中细胞凋亡途径的重要性。这些结果可用于开发 PD 治疗的新策略。

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