Roles of mitophagy and immune infiltration in Parkinson's disease: new perspectives from bioinformatics analysis and A53T transgenic mice.

BACKGROUND

Mitophagy plays a critical role in the pathology of Parkinson's disease (PD) via mitochondrial quality control, making it a promising therapeutic target. However, the precise mechanistic role of mitophagy in PD pathogenesis and progression remains unclear.

METHODS

We conducted a bioinformatic analysis to identify hub mitophagy-related differentially expressed genes (hub-MPDEGs). The mRNA expression levels of these identified genes were validated using two single-cell RNA sequencing datasets (GSE178265 and PRJNA1145007) and further confirmed in an α-synuclein A53T transgenic mouse model.

RESULTS

Five hub-MPDEGs were identified: CANX, GABARAPL1, HSPD1, PPARGC1A, and TOMM20. Transcriptomic analysis revealed elevated abundance of these genes in α-synuclein A53T mice compared to controls. Single-cell resolution analysis demonstrated significant differential expression of these genes in astrocytes, dopamine neurons, glutamatergic neurons, endothelial cells, and oligodendrocyte precursor cells within the substantia nigra of PD samples compared to controls. Furthermore, significant differences in mRNA levels were observed in peripheral immune cells, specifically CD4+ T cells, CD8+ T cells, monocytes, and NK cells, between control and PD samples.

CONCLUSIONS

This study identifies and validates five key mitophagy-related genes that are differentially regulated in the central nervous system and peripheral immune cells in the context of Parkinson's disease. These findings highlight the systemic nature of mitophagy dysregulation in PD.