A pathogenic Tau mutation drives autophagy-lysosome dysfunction that limits Tau degradation in a model of frontotemporal dementia - PubMed
6 hours ago
- #Autophagy-Lysosome Pathway
- #Tauopathy
- #Frontotemporal Dementia
- A pathogenic Tau mutation (MAPT p.R406W) disrupts autophagy-lysosome function in human neurons, leading to impaired Tau degradation.
- Mutant Tau neurons show dysfunctional lysosomes with accumulated Tau, reduced lysosome motility, and impaired autophagosome-lysosome fusion.
- Pharmacological enhancement of autophagy improves cargo clearance and lowers Tau levels but does not restore lysosomal motility defects.
- The findings suggest boosting autophagy could help restore Tau homeostasis in tauopathies like frontotemporal dementia.