Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease - PubMed

6 hours ago

Parkinson's disease (PD) is a neurodegenerative disorder affecting individuals over 60, primarily due to dopaminergic neuron deterioration in the substantia nigra.
Aging is a significant risk factor for PD, but the specific mechanisms linking aging and PD pathology remain unclear.
The study uses single-nucleus multiome sequencing to analyze transcriptomic and epigenetic profiles from 40,125 cells in the aging mouse substantia nigra.
Age-associated changes were identified at a cell type-specific level, with certain genes increasingly expressed with age and enriched in PD-related pathways, particularly in oligodendrocytes.
Integration with public PD single-cell RNA-seq datasets revealed 85 genes consistently differentially expressed in both aging and PD.
Key genes like Hsp90aa1 and Hsp90ab1 were upregulated in oligodendrocytes, microglia, and glutamatergic neurons at late aging stages.
Apoe in microglia and protein folding-related genes in oligodendrocytes were upregulated, while myelination-related genes were downregulated in oligodendrocytes at early aging stages.
The study highlights substantial regulatory network changes during aging that may predispose to PD, offering insights into PD pathogenesis and potential therapeutic targets.

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