TRIM32-UBQLN2-p62 axis promotes TDP-43 inclusion formation and amyloid aggregation through shuttle condensates - PubMed
3 hours ago
- #TDP-43
- #Neurodegeneration
- #Protein Aggregation
- The TRIM32-UBQLN2-p62 axis promotes TDP-43 inclusion formation and amyloid aggregation via shuttle condensates.
- Aberrant protein aggregation is common in ALS, FTLD, AD, and LATE, suggesting shared pathological mechanisms.
- TRIM32, UBQLN2, and p62 form condensates that capture client proteins like TDP-43 and ANXA11, modulating their mobility.
- A hydrophobic loop in TRIM32 mimics motifs in ANXA11 and TDP-43, enabling selective retention via UBQLN2 STI1 domain.
- TRIM32 condensates promote TDP-43 amyloid aggregation, worsened by pathogenic UBQLN2 mutations.
- TRIM32 co-localizes with pathological pTDP-43 inclusions in neurodegenerative disease brains, supporting its role in TDP-43 proteinopathy.