Lysophagy protects against ANXA11 amyloid fibril toxicity and propagation in FTLD - PubMed
4 hours ago
- #ANXA11
- #Neurodegeneration
- #Lysophagy
- ANXA11 aggregates are pathological in ALS/FTLD, but their toxicity and spread mechanisms are unclear.
- ANXA11 fibrils, especially mutant D40G, accumulate in lysosomes, causing membrane permeabilization (LMP) and mitochondrial issues.
- A p38/MK2/HSP27 axis senses lysosomal damage and triggers lysophagy for protection.
- Lysophagy failure in organoids leads to ANXA11 escape, seeding, and cell-to-cell propagation.
- Targeting lysophagic flux could be a therapeutic strategy for FTLD/ALS.