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遗传与生化研究进展:揭示帕金森病神经退行性变的病因发病机制。

Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson's Disease.

机构信息

Department of Pharmacy, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India.

Department of Pharmaceutical Sciences, Mohan Lal Sukhadia University, Udaipur 313001, Rajasthan, India.

出版信息

Biomolecules. 2024 Jan 5;14(1):73. doi: 10.3390/biom14010073.

Abstract

Parkinson's disease (PD) is the second most prevalent neurodegenerative movement disorder worldwide, which is primarily characterized by motor impairments. Even though multiple hypotheses have been proposed over the decades that explain the pathogenesis of PD, presently, there are no cures or promising preventive therapies for PD. This could be attributed to the intricate pathophysiology of PD and the poorly understood molecular mechanism. To address these challenges comprehensively, a thorough disease model is imperative for a nuanced understanding of PD's underlying pathogenic mechanisms. This review offers a detailed analysis of the current state of knowledge regarding the molecular mechanisms underlying the pathogenesis of PD, with a particular emphasis on the roles played by gene-based factors in the disease's development and progression. This study includes an extensive discussion of the proteins and mutations of primary genes that are linked to PD, including α-synuclein, , , , , DJ-1, and Parkin. Further, this review explores plausible mechanisms for DAergic neural loss, non-motor and non-dopaminergic pathologies, and the risk factors associated with PD. The present study will encourage the related research fields to understand better and analyze the current status of the biochemical mechanisms of PD, which might contribute to the design and development of efficacious and safe treatment strategies for PD in future endeavors.

摘要

帕金森病(PD)是全球第二大常见的神经退行性运动障碍疾病,主要表现为运动障碍。尽管几十年来提出了多种假说来解释 PD 的发病机制,但目前尚无有效的治疗方法或有前景的预防疗法。这可能归因于 PD 的复杂病理生理学和分子机制尚不清楚。为了全面应对这些挑战,全面的疾病模型对于深入了解 PD 的潜在发病机制至关重要。本综述详细分析了 PD 发病机制的分子机制的最新知识状态,特别强调了基因因素在疾病发展和进展中的作用。本研究包括对与 PD 相关的主要基因的蛋白质和突变的广泛讨论,包括α-突触核蛋白、LRRK2、PINK1、Parkin、DJ-1 和 Parkin。此外,本综述还探讨了 DA 能神经丢失、非运动和非多巴胺能病理以及与 PD 相关的风险因素的可能机制。本研究将鼓励相关研究领域更好地了解和分析 PD 的生化机制的现状,这可能有助于未来设计和开发有效的、安全的 PD 治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f859/10813470/ec04b0ade160/biomolecules-14-00073-g001.jpg

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