A metallothionein mimetic peptide protects neurons against kainic acid-induced excitotoxicity.
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.
Sonn
Katrin
K
Protein Laboratory, Department of Neuroscience and Pharmacology, Panum Institute, Copenhagen, Denmark.
Pankratova
Stanislava
S
Korshunova
Irina
I
Zharkovsky
Alexander
A
Bock
Elisabeth
E
Berezin
Vladimir
V
Kiryushko
Darya
D
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D008668:Metallothionein / Q000819:agonists* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010455:Peptides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology
C550242:EmtinB peptide; D036341:Intercellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010455:Peptides; D008668:Metallothionein; D007608:Kainic Acid