Tet2 loss and enhanced ciliogenesis suppress α-synuclein pathology.

ABSTRACT: There are no approved treatments that slow Parkinson's disease (PD) progression and therefore it is important to identify novel pathogenic mechanisms that can be targeted. Loss of the epigenetic marker, Tet2 appears to have some beneficial effects in PD models, but the underlying mechanism of action is not well understood. We performed an unbiased transcriptomic analysis of cortical neurons isolated from patients with PD to identify dysregulated pathways and determine their potential contributions to the disease process. We discovered that genes associated with primary cilia, non-synaptic sensory and signaling organelles, are upregulated in both early and late stage PD patients. Enhancing ciliogenesis in primary cortical neurons via sonic hedgehog signaling suppressed the accumulation of α

SUBMITTER: Quansah E 

PROVIDER: S-EPMC11974201 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature