Lianping Gu, Xu Wang, Yaohua Liu, Hongyu Tang, Jingyan Gu, Wei Wang, Xiaowen Lu and Meiqing Lou* Pages 1 - 20 ( 20 )
Background: Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder globally, with its etiology intricately linked to a complex interplay of genetic predispositions and environmental factors.
Methods: A comprehensive comparative analysis of the substantia nigra transcriptome between patients with PD and controls, utilizing data from the Gene Expression Omnibus (GEO) repository, enabled the identification and validation of key hub genes associated with PD. This analysis was further substantiated at the single-cell level. The study identified four candidate chemicals potentially interacting with the proteins encoded by these hub genes, followed by molecular docking to evaluate binding affinities.
Results: DDC, KCNJ6, SLC18A2, and SLC6A3 were identified as central to PD pathology, with Benzo(a)pyrene, bisphenol A, Valproic Acid, and Fulvestrant as corresponding chemical agents. Molecular docking demonstrated Benzo(a)pyrene’s highest binding affinity, with SLC6A3 emerging as the most vulnerable target among the hub genes.
Conclusions: These findings underscore the roles of DDC, KCNJ6, SLC18A2, and SLC6A3 in PD’s molecular mechanisms, potentially modulated by the identified chemicals, with Benzo(a)pyrene highlighted as a significant environmental toxin. This study offers novel insights into the genetic and environmental determinants of PD, advancing our understanding of its etiology.
Parkinson's disease, environmental toxin, substantia nigra, GEO, bioinformatics analysis, interactional chemicals, molecular docking.