title: Protein SUMOylation, an emerging pathway in amyotrophic lateral sclerosis.
abstract: The covalent attachment of SUMO proteins (small ubiquitin-like modifier) to specific proteins or SUMOylation regulates their functional properties in the nucleus and cytoplasm of neurons. Recent studies reported dysfunction of the SUMO pathway in molecular and cellular abnormalities associated with amyotrophic lateral sclerosis (ALS). Furthermore, several observations support a direct role for SUMOylation in diverse pathogenic mechanisms involved in ALS, such as response to hypoxia, oxidative stress, glutamate excitotoxicity and proteasome impairment. Recent results also suggest that SUMO modifications of superoxide dismutase 1, transactive response DNA-binding protein 43, CTE (COOH terminus of EAAT2) (proteolytic C-terminal fragment of the glutamate transporter excitatory amino acid transporter 2, EAAT2) and proteins regulating the turnover of ALS-related proteins can participate in the pathogenesis of ALS. Moreover, the fused in sarcoma (FUS) gene, mutated in ALS, encodes a protein with a SUMO E3 ligase activity. In this review, we summarize the functioning of the SUMO pathway in normal conditions and in response to stresses, its action on ALS-related proteins and discuss the need for further research on this pathway in ALS.
authors.affiliation: UMR INSERM U930, Université François-Rabelais, Tours, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Dangoumau
authors.forename: Charlotte
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.forename: Hélène
authors.initials: H
authors.lastname: Blasco
authors.forename: Julien
authors.initials: J
authors.lastname: Praline
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction; D058207:Sumoylation; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1