A Metallothionein Mimetic Peptide Protects Neurons Against Kainic Acid-Induced Excitotoxicity

作者：Sonn Katrin; Pankratova Stanislava; Korshunova Irina; Zharkovsky Alexander; Bock Elisabeth; Berezin Vladimir; Kiryushko Darya^*

来源：Journal of Neuroscience Research, 2010, 88(5): 1074-1082.

DOI：10.1002/jnr.22281

• MT
• neuroprotection
• kainate
• brain injury

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 beta-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.

• 出版日期2010-4