Pappu Md Al Amin, Alamin Md, Sultana Most Humaira, Azad Akm, Auwul Md Rabiul, Mahmud Sabkat, Ajadee Alvira, Sarker Arnob, Alyami Salem A, Mollah Md Nurul Haque
Bioinformatics Lab (Dry), Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh.
Department of Mathematics and Physics, School of Engineering & Physical Sciences, North South University, Dhaka, 1229, Bangladesh.
Sci Rep. 2025 Jul 25;15(1):27086. doi: 10.1038/s41598-025-09417-w.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, characterized by progressive motor and cognitive decline, leading to long-term disability and significantly impacting quality of life. While PD research has traditionally focused on dopaminergic neurons in the substantia nigra (SN), emerging evidence also suggests glial involvement in disease progression. So, this study explored PD-associated key genes from neuronal and glial cell types to uncover pathogenetic mechanisms and potential therapeutics by employing single-nucleus RNA sequencing (snRNA-seq) data from the accession number GSE184950. A total of 426,886 nuclei were analyzed, yielding 129,473 high-quality nuclei. Through rigorous quality control, clustering, and marker gene analysis using scVI and Scanpy, nine distinct cell types were delineated, including neurons, astrocytes, and microglia. 18 common differentially expressed genes (cDEGs) were identified across neuronal and glial cell types. Gene ontology (GO) and KEGG enrichment analyses revealed key terms associated with neurodegeneration, including PD. A total of six critical KGs, including HSPA1A, DNAJB1, BAG3, SYN1, CALB2, and NEFL, along with their key regulators, were identified by the protein-protein interaction network. Finally, three repurposed drugs (Celastrol, Withaferin-A, and Apomorphine) were suggested as the therapeutics agents for PD by molecular docking. In-silico ADME/T analyses were conducted using pkCSM and SwissADME to evaluate the pharmacokinetic properties of these compounds. These findings could shed light on PD mechanisms and hold promise for advancing diagnostics and therapies.
帕金森病（PD）是第二常见的神经退行性疾病，其特征是进行性运动和认知功能衰退，导致长期残疾并严重影响生活质量。虽然PD研究传统上集中于黑质（SN）中的多巴胺能神经元，但新出现的证据也表明神经胶质细胞参与了疾病进展。因此，本研究通过利用登录号为GSE184950的单核RNA测序（snRNA-seq）数据，探索了神经元和神经胶质细胞类型中与PD相关的关键基因，以揭示发病机制和潜在的治疗方法。共分析了426,886个细胞核，得到129,473个高质量细胞核。通过使用scVI和Scanpy进行严格的质量控制、聚类和标记基因分析，划分出九种不同的细胞类型，包括神经元、星形胶质细胞和小胶质细胞。在神经元和神经胶质细胞类型中鉴定出18个常见的差异表达基因（cDEG）。基因本体（GO）和KEGG富集分析揭示了与神经退行性变相关的关键术语，包括PD。通过蛋白质-蛋白质相互作用网络鉴定出总共六个关键基因（KG），包括HSPA1A、DNAJB1、BAG3、SYN1、CALB2和NEFL，以及它们的关键调节因子。最后，通过分子对接提出三种重新利用的药物（雷公藤红素、醉茄素A和阿扑吗啡）作为PD的治疗药物。使用pkCSM和SwissADME进行了计算机辅助的ADME/T分析，以评估这些化合物的药代动力学性质。这些发现可以阐明PD的机制，并有望推动诊断和治疗的进展。
