Presenilin-dependent regulation of neuronal tau pathology via the autophagy and proteasome pathways - PubMed
5 hours ago
- #Autophagy
- #Tau pathology
- #Alzheimer’s disease
- Presenilin (PS/PSEN) mutations cause early-onset familial Alzheimer's disease (AD) by increasing amyloid-β (Aβ) peptides and tau pathology.
- The study explores how PS dysfunction leads to tau pathology via autophagy and proteasome pathways.
- Findings show elevated phosphorylated tau (pTau) and ubiquitin factor p62 in familial AD-linked PSEN1 mutation carriers, indicating disrupted proteasomal degradation.
- Human iPSC-derived neurons with PSEN1 G206D mutation showed increased aggregated tau and reduced secreted tau.
- Proteasomal inhibition reduced intracellular tau and pTau while promoting tau release, partially dependent on PS.
- Neuronal PS-deficient mice exhibited Akt activation, GSK3β inhibition, and elevated tau and p62 levels.
- PS function is crucial for autophagy/proteasome-mediated tau clearance, with PSEN1 mutations disrupting these pathways.