Insights from Single-Cell RNA-seq: Identifying the Actin Gene Family as Novel Drivers in Parkinson’s Disease

Abstract

Background. Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting millions of individuals worldwide. The complex etiology of PD involves a combination of genetic and environmental factors. The Actin family encompasses a group of highly conserved cytoskeletal proteins that play a crucial role in maintaining cellular structure and function. Actin proteins are involved in various cellular processes, including cell motility, vesicle trafficking, and synaptic transmission. This paper delves into the exploration of the Actin family of genes, revealing their potential as key contributors to PD through the application of single-cell RNA-seq. Method. We obtained single-cell transcriptomes (GSE237133) from the NIH portal website. We conducted an extensive comparative analysis of single-cell transcriptomes derived from Parkinson's disease organoids and two control organoids to identify differentially expressed genes, pathways, and gene ontology terms. Results. We conducted a comparative analysis of single-cell transcriptomes from Parkinson's disease organoid and two control organoids, aiming to identify differentially expressed genes, pathways, and gene ontology items. In comparing the PD organoid with the control organoid, we observed that the ACTB and ACTG1 genes were common among 18 of the top 20 upregulated KEGG pathways and among 15 of the top 20 upregulated Reactome pathways. Additionally, when comparing the PD organoid with the isogenic control organoid, we found the ACTB and ACTG1 genes shared among 19 out of the top 20 pathways and among 19 out of the top 20 upregulated Reactome pathways. An additional noteworthy finding includes the overexpression of several Mitochondrially Encoded NADH family genes in the PD organoid cells compare to the control organoids cells. Conclusion. The Actin family of genes in general and ACTB and ACTG1 genes in particular emerges as a potential new player in the convoluted landscape of Parkinson disease. Further research is needed to elucidate the precise mechanisms through which Actin dysregulation contributes to PD pathology and to develop targeted therapeutic approaches. Unraveling the connections between Actin and PD may pave the way for innovative strategies to intervene in the disease process, ultimately improving the lives of individuals affected by Parkinson's disease.