作为帕金森病治疗靶点的非编码 RNA:聚焦多巴胺

IF 2.9 4区 医学 Q2 PATHOLOGY Pathology, research and practice Pub Date : 2024-10-03 DOI:10.1016/j.prp.2024.155641
Khalid Saad Alharbi
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引用次数: 0

摘要

帕金森病是一种高度复杂的神经系统疾病,主要表现为多巴胺能神经元的丧失。尽管有大量药物可以缓解症状,但仍迫切需要针对帕金森病根本病理的新疗法。非编码 RNA 在基因调控和各种细胞过程中的作用日益重要,并被发现在帕金森病的病理生理学中发挥作用。本综述分析了不同的 ncRNA 与多巴胺信号传导的交叉作用。我们试图限制可激活多巴胺分泌的各种 ncRNA 网络。首先,我们描述了以多巴胺受体为靶点并与帕金森病有关的 miRNA 的失调。接下来,我们将讨论 lncRNA 在多巴胺能神经元中的功能以及与帕金森病易感基因的联系。最后,我们将分析新型 circRNA(如 ciRS-7),它们可能会调节与多巴胺相关的过程并作为可能的帕金森病生物标志物。在这篇综述中,我们将介绍多巴胺神经元复苏治疗帕金森病的最新进展以及 ncRNA 的治疗潜力。本综述批判性地评估了现有数据,并预测了一些 ncRNA(如 PTBP1)在未来成为候选治疗靶点的作用。因此,本综述旨在总结帕金森病多巴胺信号传导不足的分子原因,并指出神经科学中与 ncRNA 相关的新型治疗方向。
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Non-coding RNAs as therapeutic targets in Parkinson’s Disease: A focus on dopamine
Parkinson’s Disease is a highly complicated neurological disorder, with a key manifestation of loss of dopaminergic neurons. Despite the plethora of medicines that alleviate the symptoms, there is an urgent need for new treatments acting on the fundamental pathology of PD. Non-coding RNAs are becoming increasingly important in gene regulation and various cellular processes and are found to play a role in PD pathophysiology. This review analyzes the cross-talk of distinct ncRNAs with dopamine signaling. We attempt to constrain the various ncRNA networks that can activate dopamine production. First, we describe the deregulation of miRNAs that target dopamine receptors and have been implicated in PD. Next, we turn to the functions of lncRNAs in dopaminergic neurons and the connections to susceptibility genes for PD. Finally, we will analyze the novel circRNAs, such as ciRS-7, which may modulate dopamine-linked processes and serve as possible PD biomarkers. In this review, we describe recent progress in dopamine neuron revival to treat PD and the therapeutic potential of ncRNA. This review critically evaluates the available data, and we predict the role of some ncRNAs, such as PTBP1, to become candidate treatment targets in the future. Thus, this review aims to summarize the molecular causes for the deficit in dopamine signaling in PD and point to novel ncRNAs-linked therapeutic directions in neuroscience.
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来源期刊
CiteScore
5.00
自引率
3.60%
发文量
405
审稿时长
24 days
期刊介绍: Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.
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