Horoufi Sara Taremi, Zaeifi Davood
Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Science, Tehran, Iran.
Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Azadi Sq, Mashhad, 9177899191, Khorasan Razavi, Iran.
Mol Neurobiol. 2025 Jul 2. doi: 10.1007/s12035-025-05182-z.
Parkinson's disease (PD) is a complex disease influenced by both genetic and environmental factors. Despite advances in understanding PD genetics, subtype-specific mechanisms remain poorly characterized. This study aims to identify distinct genetic markers and pathways across PD subtypes, addressing this gap to enable targeted diagnostics and therapies. Genes associated with PD were collected from various databases and categorized into groups based on the PD type to assess the PD risk. Protein interaction analysis was conducted to identify functional clusters and key genes within each group. KEGG enrichment analysis revealed common genes and pathways among the different PD groups. This study conformed to the PRISMA 2020 guidelines for systematic data collection and analysis. Hub genes such as PRKN, SNCA, and LRRK2 have demonstrated considerable potential as biomarkers for genetic predisposition in PD, alongside the identification of additional complementary genes. Analysis of hub node variants highlighted specific genetic variations in these genes. We identified several microRNAs, including hsa-miR-335-5p, hsa-miR-19a-3p, and hsa-miR-106a-5p, as well as transcription factors that interact with crucial hub genes. This study refines subtype-specific mechanisms for established PD genes and identifies novel genetic markers and pathways associated with juvenile, young-onset, late-onset, familial, and sporadic Parkinson's disease, enhancing our understanding of their molecular mechanisms and potential for targeted diagnostics and therapies. Specifically, we highlight the roles of hub genes, such as PRKN, SNCA, and LRRK2, alongside significant microRNA interactions, which may serve as biomarkers for early detection and personalized treatment approaches.
帕金森病(PD)是一种受遗传和环境因素共同影响的复杂疾病。尽管在理解PD遗传学方面取得了进展,但亚型特异性机制仍未得到充分表征。本研究旨在识别不同PD亚型的独特遗传标记和途径,填补这一空白,以实现靶向诊断和治疗。从各种数据库中收集与PD相关的基因,并根据PD类型进行分组,以评估PD风险。进行蛋白质相互作用分析,以识别每组中的功能簇和关键基因。KEGG富集分析揭示了不同PD组之间的共同基因和途径。本研究符合PRISMA 2020系统数据收集和分析指南。诸如PRKN、SNCA和LRRK2等枢纽基因已显示出作为PD遗传易感性生物标志物的巨大潜力,同时还鉴定了其他互补基因。对枢纽节点变异的分析突出了这些基因中的特定遗传变异。我们鉴定了几种 microRNA,包括hsa-miR-335-5p、hsa-miR-19a-3p和hsa-miR-106a-5p,以及与关键枢纽基因相互作用的转录因子。本研究完善了已确定的PD基因的亚型特异性机制,并识别了与青少年、早发型、晚发型、家族性和散发性帕金森病相关的新型遗传标记和途径,加深了我们对其分子机制以及靶向诊断和治疗潜力的理解。具体而言,我们强调了枢纽基因(如PRKN、SNCA和LRRK2)的作用,以及重要的microRNA相互作用,它们可能作为早期检测和个性化治疗方法的生物标志物。