SUMO-1 conjugation blocks beta-amyloid-induced astrocyte reactivity.

Abstract

Astrocyte reactivity is implicated in the neuronal loss underlying Alzheimer's disease. Curcumin has been shown to reduce astrocyte reactivity, though the exact pathways underlying these effects are incompletely understood. Here we investigated the role of the small ubiquitin-like modifier (SUMO) conjugation in mediating this effect of curcumin. In beta-amyloid (Aβ)-treated astrocytes, morphological changes and increased glial fibrillary acidic protein (GFAP) confirmed reactivity, which was accompanied by c-jun N-terminal kinase activation. Moreover, the levels of SUMO-1 conjugated proteins, as well as the conjugating enzyme, Ubc9, were decreased, with concomitant treatment with curcumin preventing these effects. Increasing SUMOylation in astrocytes, by over-expression of constitutively active SUMO-1, but not its inactive mutant, abrogated Aβ-induced increase in GFAP, suggesting astrocytes require SUMO-1 conjugation to remain non-reactive.