Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy - PubMed
7 hours ago
- #Autophagy
- #TDP-43
- #Neurodegeneration
- TDP-43 proteinopathy is linked to diseases like ALS, FTD, and LATE due to cytoplasmic TDP-43 aggregates.
- Autophagy-lysosome pathway (ALP) and UPS failure in clearing TDP-43 aggregates may be due to sequestration of key components.
- Classical autophagic activators (e.g., rapamycin) are limited in addressing downstream flux bottlenecks for TDP-43 clearance.
- New strategies include TFEB activators, PROTACs, and antisense oligonucleotides to restore autophagic flux.
- Multi-targeting approaches and better biomarkers are proposed for improving clinical outcomes in neurodegenerative diseases.