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非编码 RNA 及其对多巴胺能神经元的影响:帕金森病中的自噬途径。

ncRNAs and their impact on dopaminergic neurons: Autophagy pathways in Parkinson's disease.

机构信息

Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.

Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia.

出版信息

Ageing Res Rev. 2024 Jul;98:102327. doi: 10.1016/j.arr.2024.102327. Epub 2024 May 10.

Abstract

Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.

摘要

帕金森病(PD)是一种复杂的神经疾病,由于黑质中多巴胺能神经元的逐渐丧失,导致严重的运动和非运动症状。PD 的病因受多种遗传、环境和细胞变量的影响。这种病理生理学的一个重要方面是自噬,这是一种关键的细胞内稳态过程,可分解和回收细胞质成分。基因组技术的最新进展揭示了 ncRNAs 对自噬途径调节的重要影响,从而暗示它们在 PD 的发病和进展中的作用。它们是 RNA 家族的成员,包括 miRNA、circRNA 和 lncRNA,这些 RNA 已被证明通过调节与自噬活性和多巴胺能神经元存活相关的基因的表达,在 PD 的发病机制中发挥新的多效性功能。本综述旨在将当前的遗传范式与自噬相关 ncRNAs 在 PD 中的治疗前景相结合。通过综合最近遗传研究的发现,我们强调了 ncRNAs 在自噬调节中的重要性,它们在 PD 中的失调方式,以及它们如何为治疗干预提供新的维度。还讨论了针对 PD 中 ncRNAs 的治疗潜力,包括需要克服的障碍和必须接受的未来方向,以便将这些 ncRNA 分子用于 PD 的治疗和管理。

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