Hippocampal mitophagy alterations in MAPT-associated frontotemporal dementia with parkinsonism.

ABSTRACT: The enzyme pair PINK1 and PRKN together orchestrates a cytoprotective mitophagy pathway that selectively tags damaged mitochondria with phospho-serine 65 ubiquitin (pS65-Ub) and directs them for autophagic-lysosomal degradation (mitophagy). We previously demonstrated a significant accumulation of pS65-Ub signals in autopsy brains of sporadic Lewy body disease and Alzheimer's disease cases, which strongly correlated with early tau pathology. In this study, we extended our analysis to a series of pathologically confirmed cases of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) harboring different pathogenic mutations in MAPT, the gene encoding tau. We assessed the morphology, levels, and distribution of the mitophagy tag pS65-Ub in several affected brain regions a

SUBMITTER: Richardson T 

PROVIDER: S-EPMC11849217 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature