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Lookup NU author(s): Ryley Parrish, Dr Alistair Jenkins, Mark Cunningham
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© 2019 Elsevier Inc. Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder. O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates. The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification. The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity. We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue. Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control. These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
Author(s): Sanchez RG, Parrish RR, Rich M, Webb WM, Lockhart RM, Nakao K, Ianov L, Buckingham SC, Broadwater DR, Jenkins A, de Lanerolle NC, Cunningham M, Eid T, Riley K, Lubin FD
Publication type: Article
Publication status: Published
Journal: Neurobiology of Disease
Year: 2019
Volume: 124
Pages: 531-543
Print publication date: 01/04/2019
Online publication date: 06/01/2019
Acceptance date: 01/01/2019
ISSN (print): 0969-9961
ISSN (electronic): 1095-953X
Publisher: Academic Press Inc.
URL: https://doi.org/10.1016/j.nbd.2019.01.001
DOI: 10.1016/j.nbd.2019.01.001
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