SUMO1 Modification of Tau in Progressive Supranuclear Palsy

Small ubiquitin-like modifiers (SUMO) have been implicated in several neurodegenerative diseases. SUMO1 conjugation has been shown to promote aggregation and regulate phosphorylation of the tau protein linked to Alzheimer's disease and related tauopathies. The current study has demonstrated that SUMO1 co-localizes with intraneuronal tau inclusions in progressive supranuclear palsy (PSP). Immunoprecipitation of isolated and solubilized tau fibrils from PSP tissues revealed SUMO1 conjugation to a cleaved and N-terminally truncated tau. The effects of SUMOylation were examined using tau-SUMO fusion proteins which showed a higher propensity for tau oligomerization of PSP-truncated tau and accumulation on microtubules as compared to the full-length protein. This was found to be specific for SUMO1 as the corresponding SUMO2 fusion protein did not display a significantly altered cytoplasmic distribution or aggregation of tau. Blocking proteasome-mediated degradation promoted the aggregation of the tau fusion proteins with the greatest effect observed for truncated tau-SUMO1. The SUMO1 modification of the truncated tau in PSP may represent a detrimental event that promotes aggregation and impedes the ability of cells to remove the resulting protein deposits. This combination of tau truncation and SUMO1 modification may be a contributing factor in PSP pathogenesis.

Automated summary

The study suggests that SUMO1 conjugation with tau protein in progressive supranuclear palsy (PSP) promotes aggregation and impedes removal of protein deposits. The fusion of truncated tau with SUMO1 leads to increased oligomerization and accumulation on microtubules, while SUMO2 fusion protein does not show significant alteration in cytoplasmic distribution or tau aggregation. Blocking proteasome-mediated degradation enhances aggregation of tau-SUMO1 fusion protein, indicating that SUMO1 modification of truncated tau may contribute to PSP pathogenesis.