PMID- 29489588
OWN - NLM
STAT- MEDLINE
DCOM- 20190405
LR  - 20190405
IS  - 1473-558X (Electronic)
IS  - 0959-4965 (Linking)
VI  - 29
IP  - 5
DP  - 2018 Mar 21
TI  - Disruption of the GluA2/GAPDH complex using TAT-GluA2NT1-3-2 peptide protects 
      against AMPAR-mediated excitotoxicity after epilepsy.
PG  - 432-439
LID - 10.1097/WNR.0000000000000996 [doi]
AB  - Excitotoxicity and neuronal death following epilepsy involve 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). It forms 
      a protein complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and 
      co-internalizes upon activation of AMPA receptors after epilepsy. Disruption of 
      the GluA2/GAPDH complex with an interfering peptide, TAT-GluA2NT1-3-2, protects 
      cells against AMPAR-mediated excitotoxicity, which have been identified in 
      in-vitro and in-vivo models of brain ischemia. We postulated that disruption of 
      the GluA2/GAPDH interaction with the TAT-GluA2NT1-3-2 peptide would also protect 
      against AMPAR-induced neuronal injury in an in-vivo model of status epilepticus 
      (SE). In the present study, we divided pilocarpine-induced SE Wistar rats into 
      three main groups: the TAT-GluA2NT1-3-2 peptide group, the TAT-GluA2NT-scram 
      peptide group, and the normal saline group, and injected different doses of 
      peptides stereotaxically into the hippocampus of SE rats to investigate whether 
      the GluA2/GAPDH interaction could be disrupted by our TAT-GluA2NT1-3-2 peptide 
      and determine its most appropriate dose. Then, the dose was administered 
      stereotaxically at different time points after SE to determine the best 
      administration time of neuronal protection. We found that the TAT-GluA2NT1-3-2 
      peptide can disrupt the GluA2/GAPDH interaction and protects against 
      epilepsy-induced neuronal damage. The GluA2/GAPDH interaction may be a novel 
      therapeutic target for epilepsy.
FAU - Zhang, Jinghui
AU  - Zhang J
AD  - Department of Pediatrics, Qilu Hospital of Shandong University.
FAU - Qiao, Nana
AU  - Qiao N
AD  - Department of Pediatrics, Qilu Hospital of Shandong University.
FAU - Ding, Xiufang
AU  - Ding X
AD  - Department of Pediatrics, Jinan Children's Hospital, Jinan, Shandong.
FAU - Wang, Jiwen
AU  - Wang J
AD  - Department of Neurology, Shanghai Children's Medical Center, Shanghai Jiaotong 
      University School of Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (Anticonvulsants)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptides)
RN  - 0 (Receptors, AMPA)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - P6W5IXV8V9 (glutamate receptor ionotropic, AMPA 2)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/*pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Epilepsy/*drug therapy/*metabolism/pathology
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism
MH  - Hippocampus/drug effects/metabolism/pathology
MH  - Male
MH  - Neurons/drug effects/metabolism/pathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Peptides/*pharmacology
MH  - Pilocarpine
MH  - Rats, Wistar
MH  - Receptors, AMPA/metabolism
EDAT- 2018/03/01 06:00
MHDA- 2019/04/06 06:00
CRDT- 2018/03/01 06:00
PHST- 2018/03/01 06:00 [entrez]
PHST- 2018/03/01 06:00 [pubmed]
PHST- 2019/04/06 06:00 [medline]
AID - 00001756-201803020-00015 [pii]
AID - 10.1097/WNR.0000000000000996 [doi]
PST - ppublish
SO  - Neuroreport. 2018 Mar 21;29(5):432-439. doi: 10.1097/WNR.0000000000000996.