Objective: In this study, we analyzed transcriptome data regarding protein degradation pathways and inflammation sourced from GEO database.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease, characterized by dysregulation in abnormal protein accumulation and neuroinflammation. In this study, we analyzed transcriptome data regarding protein degradation pathways and inflammation sourced from GEO database.

Method: The GEO database was screened for datasets containing gene expression information derived from the substantia nigra of both PD patients and control cohorts. Our selection narrowed down to two datasets: GSE8397 and GSE20292. The “Combat” algorithm was applied to adjust for any discrepancies between batches. Differentially expressed genes (DEGs) between PD patients and controls were identified using the “limma” package in R. Subsequently, GO/KEGG pathway enrichment analysis was conducted. Finally, immune infiltration analysis was performed based on 29 immune cell types to reflect the infiltration of these cells into the substantia nigra in PD. All analyses were performed in R language (version 4.3.2).

Results: The DEGs identified in PD patients differed from healthy control (HC), mirroring several previous publications on PD biomarkers. Notably, DDR1 and HSPA6 displayed downregulation (Fig. 1A). Among the 4036 DEGs identified in this analysis (p<0.05), genes regarding immune and protein degradation, CCL5 (linked to the immune response) and UBA7, PSMB5 (related to proteasome activity) showed significant decreases in expression. Subsequent GO/KEGG analysis revealed a noticeable shift in the proteasome pathway (Fig 1B, D). Finally, the immune filtration analysis showed clear differences in immune cell populations between PD and HC groups, with a marked increase in HLA expression in PD patients (Fig. 1C).

Conclusion: The observed alterations in gene expression pertaining to immune and proteasomal pathways offer insights into their contributory roles in PD.

Transcriptome analysis results

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MDS Abstracts - https://www.mdsabstracts.org/abstract/transcriptome-analysis-of-proteasome-and-inflammation-in-the-substantia-nigra-of-parkinsons-disease-patients-the-geo-database/