Cofilin hyperphosphorylation triggers TDP-43 pathology in sporadic amyotrophic lateral sclerosis - PubMed
3 days ago
- #TDP-43
- #ALS
- #neurodegeneration
- Cofilin hyperphosphorylation is linked to TDP-43 pathology in sporadic ALS (SALS).
- TDP-43 pathology includes cytoplasmic mislocalization, inclusion formation, hyperphosphorylation, and fragmentation.
- Cofilin regulates actin dynamics; its hyperphosphorylation leads to increased F-actin and disrupted actin equilibrium.
- Hyperphosphorylated cofilin and altered actin dynamics were observed in SALS patients and TDP-43 disease models.
- Pharmacological stabilization of F-actin induced TDP-43 pathology and stress granule recruitment.
- Increased LIMK1 phosphorylation and tropomyosin isoforms 4.1/4.2 were detected in SALS patients.
- Preventing cofilin phosphorylation (e.g., via S3A peptide) may be a therapeutic strategy for ALS and other neurodegenerative diseases.