SUMO on the road to neurodegeneration

Abstract

Sumoylation is a post-translational modification by which small ubiquitin-like modifiers (SUMO) are covalently conjugated to target proteins. This reversible pathway provides a rapid and efficient way to modulate the subcellular localization, activity and stability of a wide variety of substrates. Similar to its well-known cousin ubiquitin, SUMO co-localize with the neuronal inclusions associated with several neurodegenerative diseases, including multiple system atrophy, Huntington's disease and other related polyglutamine disorders. The identification of huntingtin, ataxin-1, tau and alpha-synuclein as SUMO substrates further supports the involvement of sumoylation in the pathogenesis of this family of neurological diseases. In addition to direct targeting of these constituent proteins, sumoylation also impacts other disease pathways such as oxidative stress, protein aggregation and proteasome-mediated degradation. This review highlights the recent advances in understanding the contributions of SUMO to neurodegeneration and the underlying pathogenic mechanisms of these diseases.