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Disruption of the GluA2/GAPDH complex using TAT-GluA2NT1-3-2 peptide protects against AMPAR-mediated excitotoxicity

Jinghui Zhang1, Nana Qiao1, Xiufang Ding2

  • 1Department of Pediatrics, Qilu Hospital of Shandong University.

Neuroreport
|March 1, 2018
PubMed

Insights

A novel peptide disrupts the GluA2/GAPDH complex, protecting against epilepsy-induced neuronal death. This finding suggests targeting the GluA2/GAPDH interaction as a new therapeutic strategy for epilepsy.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Epilepsy-induced neuronal death involves alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs).
  • AMPARs form a complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), co-internalizing upon receptor activation during epilepsy.
  • Disrupting the GluA2/GAPDH complex with TAT-GluA2NT1-3-2 peptide shows promise in protecting against AMPAR-mediated excitotoxicity.

Purpose of the Study:

  • To investigate the neuroprotective effects of the TAT-GluA2NT1-3-2 peptide in an in-vivo model of status epilepticus (SE).
  • To determine the optimal dosage and administration timing of the TAT-GluA2NT1-3-2 peptide for neuronal protection.

Main Methods:

  • Pilocarpine-induced SE in Wistar rats was used as the in-vivo model.
  • Rats were divided into groups receiving TAT-GluA2NT1-3-2 peptide, a scrambled peptide, or saline.
  • Peptides were administered stereotactically into the hippocampus at varying doses and time points post-SE.

Main Results:

  • The TAT-GluA2NT1-3-2 peptide successfully disrupted the GluA2/GAPDH interaction in the hippocampus.
  • Administration of the peptide demonstrated significant protection against epilepsy-induced neuronal damage.
  • The study identified an effective dose and optimal administration window for the peptide.

Conclusions:

  • The GluA2/GAPDH interaction is a viable therapeutic target for mitigating epilepsy-related neuronal injury.
  • The TAT-GluA2NT1-3-2 peptide offers a potential novel therapeutic strategy for managing epilepsy.

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