UBQLN2 links proteotoxicity with lipid metabolism in neurodegeneration - PubMed
5 hours ago
- #Proteostasis
- #Lipid Metabolism
- #Neurodegeneration
- UBQLN2 serves as a molecular hub connecting protein quality control (proteostasis) with lipid metabolism in neurodegenerative diseases like ALS and FTD.
- UBQLN2 mutations impair the degradation of enzymes ILVBL and ALDH3A2, essential for mitochondrial lipid catabolism linked to lipid droplets and neuronal health.
- TDP-43 pathology also disrupts UBQLN2-mediated degradation of ILVBL and ALDH3A2, contributing to metabolic dysfunction and neurodegeneration.
- Restoring the UBQLN2-ILVBL/ALDH3A2 axis alleviates neurodegenerative symptoms in neurons, organoids, and mouse models.
- Findings establish UBQLN2 as a key regulator of metabolic homeostasis in ALS, FTD, and related disorders.