title: Sumoylation: Implications for Neurodegenerative Diseases.
abstract: The covalent posttranslational modifications of proteins are critical events in signaling cascades that enable cells to efficiently, rapidly and reversibly respond to extracellular stimuli. This is especially important in the CNS where the processes affecting synaptic communication between neurons are highly complex and very tightly regulated. Sumoylation regulates the function and fate of a diverse array of proteins and participates in the complex cell signaling pathways required for cell survival. One of the most complex signaling pathways is synaptic transmission.Correct synaptic function is critical to the working of the brain and its alteration through synaptic plasticity mediates learning, mental disorders and stroke. The investigation of neuronal sumoylation is a new and exciting field and the functional and pathophysiological implications are far-reaching. Sumoylation has already been implicated in a diverse array of neurological disorders. Here we provide an overview of current literature highlighting recent insights into the role of sumoylation in neurodegeneration. In addition we present a brief assessment of drug discovery in the analogous ubiquitin system and extrapolate on the potential for development of novel therapies that might target SUMO-associated mechanisms of neurodegenerative disease.
authors.affiliation: Ipsen Bioinnovation Ltd, Units 4-10 The Quadrant, Barton Lane, Abingdon, OX14 3YS, UK.
authors.forename: Dina B
authors.initials: DB
authors.lastname: Anderson
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Campus Universitario - Trindade, Florianopolis, CEP, 88040-900, Brazil.
authors.forename: Camila A
authors.initials: CA
authors.lastname: Zanella
authors.affiliation: MRC Centre for Synaptic Plasticity, School of Biochemistry, University of Bristol, University Walk, Bristol, BS8 1TD, UK.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Henley
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Campus Universitario - Trindade, Florianopolis, CEP, 88040-900, Brazil. helena.cimarosti@ufsc.br.
authors.forename: Helena
authors.initials: H
authors.lastname: Cimarosti
mesh_terms: D000818:Animals; D006801:Humans; D009410:Nerve Degeneration; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation; D009435:Synaptic Transmission; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D025841:Small Ubiquitin-Related Modifier Proteins; D044767:Ubiquitin-Protein Ligases
keywords: Alzheimer’s disease; Amyotrophic lateral sclerosis; Drug targets; Ischemia; Neuronal intranuclear inclusion disease; Parkinson’s disease; Polyglutamine diseases