title: Molecular targets underlying SUMO-mediated neuroprotection in brain ischemia.
abstract: SUMOylation (small ubiquitin-like modifier conjugation) is an important post-translational modification which is becoming increasingly implicated in the altered protein dynamics associated with brain ischemia. The function of SUMOylation in cells undergoing ischemic stress and the identity of small ubiquitin-like modifier (SUMO) targets remain in most cases unknown. However, the emerging consensus is that SUMOylation of certain proteins might be part of an endogenous neuroprotective response. This review brings together the current understanding of the underlying mechanisms and downstream effects of SUMOylation in brain ischemia, including processes such as autophagy, mitophagy and oxidative stress. We focus on recent advances and controversies regarding key central nervous system proteins, including those associated with the nucleus, cytoplasm and plasma membrane, such as glucose transporters (GLUT1, GLUT4), excitatory amino acid transporter 2 glutamate transporters, K+ channels (K2P1, Kv1.5, Kv2.1), GluK2 kainate receptors, mGluR8 glutamate receptors and CB1 cannabinoid receptors, which are reported to be SUMO-modified. A discussion of the roles of these molecular targets for SUMOylation could play following an ischemic event, particularly with respect to their potential neuroprotective impact in brain ischemia, is proposed.
authors.affiliation: School of Pharmacy, Hopkins Building, University of Reading, Whiteknights, Reading, UK.
authors.forename: Vasco
authors.initials: V
authors.lastname: Silveirinha
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Stephens
authors.forename: Helena
authors.initials: H
authors.lastname: Cimarosti
mesh_terms: D002545:Brain Ischemia / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels; D018696:Neuroprotective Agents; D025841:Small Ubiquitin-Related Modifier Proteins
keywords: ion channel; neurodegeneration; receptor; small ubiquitin-like modifier; stroke; transporter