阐明与帕金森病病因的遗传变异相关的生物标志物和分子途径。

IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY
Hai Duc Nguyen
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引用次数: 0

摘要

遗传变异可以影响在帕金森病(PD)病理生理学中重要的信号通路。了解它们之间的关系对PD的诊断仪器和预防药物的开发至关重要。我们全面分析了来自68个全基因组关联研究的数据,以揭示重要的遗传变异,并阐明由遗传变异引起的帕金森病(PD)病因的分子途径。在所有68项研究中发现了6个与PD相关的常见生物标志物:SNCA、TMEM175、BST1、RIT2、LRRK2和MCCC1。SNCA(↑rs5019538和↑rs356182)、LRRK2(↑rs34637584和↑rs76904798)和SH3GL2(↑rs10756907和↓rs13294100)是PD相关的主要生物标志物。PD的临床特征,如发病年龄、认知进展、运动进展、复合进展、震颤主导和姿势不稳定步态困难,已被发现由其他生物标志物支持,包括APOE、NTRK2、SLCO1B3、SLC28A3、AQP10、SNCAIP、ANO2、CADM1、PTPRD、GPR32、GPR321、SQOR、SULT1C2、GABRG2、CYP4Z1、CDH13和FANCF。重要的证据表明,与帕金森病风险增加相关的基因变异与多巴胺产生减少、受体循环、氧化还原酶活性减少和淀粉样蛋白积累增加有关。大量证据表明,遗传变异与PD风险降低有关,这是由于突触囊泡信号传导改善、神经元突起发育、组蛋白甲基化控制和兴奋性突触后电位。此外,我们还发现了MYT1L和hsa-miR-20a-5p,这对于理解与PD相关的遗传变异至关重要。这些发现为未来针对PD的治疗方法提供了坚实的基础,重点关注与疾病相关的遗传变异和过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Elucidate biomarkers and the molecular pathways associated with genetic variants that contribute to the etiology of Parkinson's disease.

Genetic variants can affect signaling pathways that are important in the pathophysiology of Parkinson's disease (PD). Comprehending their relationship is crucial for the development of diagnostic instruments and preventative drugs for PD. We thoroughly analyzed data from 68 genome-wide association studies to uncover significant genetic variations and clarify the molecular pathways underlying the etiology of Parkinson's disease (PD) resulting from genetic variants. Six common biomarkers linked to PD were found in all 68 investigations: SNCA, TMEM175, BST1, RIT2, LRRK2, and MCCC1. SNCA (↑rs5019538 and ↑rs356182), LRRK2 (↑rs34637584 and ↑rs76904798), and SH3GL2 (↑rs10756907 and ↓rs13294100) were the main biomarkers associated with PD. The clinical traits of PD, such as age at onset, cognitive progression, motor progression, composite progression, tremor dominant, and postural instability gait difficulty, have been found to be underpinned by additional biomarkers, including APOE, NTRK2, SLCO1B3, SLC28A3, AQP10, SNCAIP, ANO2, CADM1, PTPRD, GPR32, GPR321, SQOR, SULT1C2, GABRG2, CYP4Z1, CDH13, and FANCF. Significant evidence was found linking genetic variants linked to an increased risk of PD to reduced dopamine production, receptor recycling, oxidoreductase activity, and increased amyloid-beta accumulation. Considerable evidence links genetic variations with a lower risk of PD due to improved synaptic vesicle signaling, neuron projection development, controlled histone methylation, and excitatory postsynaptic potential. Additionally, we found MYT1L and hsa-miR-20a-5p, which are essential for understanding the genetic variations linked to PD. These findings provide a solid underpinning for future therapeutic approaches aimed at PD, with a focus on the genetic variants and processes connected to the illness.

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来源期刊
Acta neurologica Belgica
Acta neurologica Belgica 医学-临床神经学
CiteScore
4.20
自引率
3.70%
发文量
300
审稿时长
6-12 weeks
期刊介绍: Peer-reviewed and published quarterly, Acta Neurologica Belgicapresents original articles in the clinical and basic neurosciences, and also reports the proceedings and the abstracts of the scientific meetings of the different partner societies. The contents include commentaries, editorials, review articles, case reports, neuro-images of interest, book reviews and letters to the editor. Acta Neurologica Belgica is the official journal of the following national societies: Belgian Neurological Society Belgian Society for Neuroscience Belgian Society of Clinical Neurophysiology Belgian Pediatric Neurology Society Belgian Study Group of Multiple Sclerosis Belgian Stroke Council Belgian Headache Society Belgian Study Group of Neuropathology
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