| Literature DB >> 30625365 |
Richard G Sánchez1, R Ryley Parrish2, Megan Rich1, William M Webb1, Roxanne M Lockhart1, Kazuhito Nakao1, Lara Ianov3, Susan C Buckingham1, Devin R Broadwater4, Alistair Jenkins5, Nihal C de Lanerolle6, Mark Cunningham2, Tore Eid6, Kristen Riley7, Farah D Lubin8.
Abstract
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.Entities:
Keywords: Electroencephalogram; Electrophysiology; Hippocampus; Magnetic resonance imaging; Mass spectrometry; O-GlcNAcylation; Post-translational modification; Thiamet-G
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Year: 2019 PMID： 30625365 PMCID： PMC6379093 DOI： 10.1016/j.nbd.2019.01.001
Source DB: PubMed Journal: Neurobiol Dis ISSN： 0969-9961 Impact factor: 5.996