Protein Disulfide Isomerase Disassembles TDP-43/G3BP1 Condensates and Antagonizes TDP-43 Pathological Aggregates - PubMed
3 hours ago
- #Protein Disulfide Isomerase
- #TDP-43
- #Neurodegenerative Diseases
- Protein disulfide isomerase (PDI) inhibits TDP-43 phase separation and disassembles TDP-43/G3BP1 condensates via its b' domain.
- Wild-type PDI reduces pathological TDP-43 mislocalization, phosphorylation, and aggregation, mitigating mitochondrial damage and neuronal toxicity.
- Aberrant PDI forms lose protective functions, promoting amyloid fibril formation in stress granules, leading to cell death in ALS and AD-TDP.
- These findings highlight PDI's role in TDP-43 pathology and suggest it as a therapeutic target for neurodegenerative diseases.