Role of Sumoylation in Neurodegenerative Diseases and Inflammation

Abstract

SUMOylation, the post-translational attachment of the small ubiquitin-related modifier (SUMO) to target proteins, is essential for proper neuronal function and has emerged as a potential target in regulating Alzheimer's, Parkinson's and polyglutamine diseases. Many of the players in those diseases have been identified as SUMO substrates, like the amyloid precursor protein and tau, α-synuclein, huntingtin or ataxin-1 and -3. Aside from modifying key players in the neurodegenerative pathways, SUMO regulates inflammation and, more specifically, neuroinflammation mediated by astrocytes and microglia, which is frequently observed in neurodegenerative disorders. Here, we present recent insights into the roles for SUMOylation in these disorders, anticipating that emerging approaches to modify the SUMOylation pathway may be promising candidate therapies.