Network analysis of α-synuclein pathology progression reveals p21-activated kinases as regulators of vulnerability.

ABSTRACT: α-Synuclein misfolding and progressive accumulation drives a pathogenic process in Parkinson's disease. To understand cellular and network vulnerability to α-synuclein pathology, we developed a framework to quantify network-level vulnerability and identify new therapeutic targets at the cellular level. Full brain α-synuclein pathology was mapped in mice over 9 months. Empirical pathology data was compared to theoretical pathology estimates from a diffusion model of pathology progression along anatomical connections. Unexplained variance in the model enabled us to derive regional vulnerability that we compared to regional gene expression. We identified gene expression patterns that relate to regional vulnerability, including 12 kinases that were enriched in vulnerable regions. Among these,

SUBMITTER: Vatsa N 

PROVIDER: S-EPMC11526907 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature