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A metallothionein mimetic peptide protects neurons against kainic acid‐induced excitotoxicity
Author(s) -
Sonn Katrin,
Pankratova Stanislava,
Korshunova Irina,
Zharkovsky Alexander,
Bock Elisabeth,
Berezin Vladimir,
Kiryushko Darya
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22281
Subject(s) - kainic acid , excitotoxicity , neuroprotection , neurotoxicity , hippocampal formation , in vivo , peptide , metallothionein , pharmacology , in vitro , neurodegeneration , chemistry , neuroscience , biochemistry , biology , medicine , toxicity , nmda receptor , glutamate receptor , receptor , microbiology and biotechnology , disease , gene , organic chemistry
Abstract Metallothioneins I and II (MTI/II) are metal‐binding proteins overexpressed in response to brain injury. Recently, we have designed a peptide, termed EmtinB, which is modeled after the β‐domain of MT‐II and mimics the biological effects of MTI/II in vitro. Here, we demonstrate the neuroprotective effect of EmtinB in the in vitro and in vivo models of kainic acid (KA)‐induced neurotoxicity. We show that EmtinB passes the blood–brain barrier and is detectable in plasma for up to 24 hr. Treatment with EmtinB significantly attenuates seizures in C57BL/6J mice exposed to moderate (20 mg/kg) and high (30 mg/kg) KA doses and tends to decrease mortality induced by the high KA dose. Histopathological evaluation of hippocampal (CA3 and CA1) and cortical areas of mice treated with 20 mg/kg KA shows that EmtinB treatment reduces KA‐induced neurodegeneration in the CA1 region. These findings establish EmtinB as a promising target for therapeutic development. © 2009 Wiley‐Liss, Inc.