Abstract
The post-translational modification of proteins is critical for the spatial and temporal regulation of signalling cascades. This is especially important in the CNS where the processes affecting differentiation, growth, targeting and communication between neurones are highly complex and very tightly regulated. In recent years it has emerged that modification of proteins by members of the SUMO (small ubiquitin-related modifier) family of proteins play key roles in neuronal function. SUMOylation involves the covalent conjugation of a member of the SUMO family to lysine residues in target proteins. Multiple nuclear and perinuclear SUMOylation targets have been reported to be involved in nuclear organisation and transcriptional regulation. In addition, a growing number of extranuclear SUMO substrates have been identified that can have important acute effects on neuronal function. The SUMOylation of both intra- and extranuclear proteins have been implicated in a diverse array of processes that have far-reaching implications for neuronal function and pathophysiology. Here we review the current understanding of the targets and consequences of protein SUMOylation in the brain and examine its established and potential involvement in a wide range of neurological and neurodegenerative diseases.