PML targets and resolves structured protein inclusions to mitigate neurodegeneration - PubMed
4 hours ago
- #protein aggregation
- #PML protein
- #neurodegeneration
- PML protein targets and resolves structured protein inclusions to mitigate neurodegeneration.
- Polyglycine (polyG) inclusions in NIID recruit disordered proteins, forming stratified condensates that disrupt nuclear protein quality control and DNA repair.
- PML recognizes and eliminates polyG inclusions via chaperone-mediated disaggregation and proteasome-dependent degradation.
- Engineered PML variants clear various aggregates, including polyG, polyGA, polyQ, TDP-43, and SOD1.
- Systemic PML delivery improves cognitive and motor deficits in NIID and TDP-43 proteinopathy mouse models.
- The study reveals a conserved spatial organization of nuclear inclusions and positions PML as a therapeutic target for protein aggregation diseases.