Open AccessOriginal Nerve Growth Factor Mimetic Dipeptide GK-2 Restores Impaired Cognitive Functions in Rat Models of Alzheimer’s Disease
Author(s) -
P. Yu. Povarnina,
O. N. Vorontsova,
Т. А. Gudasheva,
R. U. Ostrovskaya,
С. Б. Середенин
Publication year - 2013
Publication title -
acta naturae
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 26
ISSN - 2075-8251
DOI - 10.32607/20758251-2013-5-3-84-91
Subject(s) - neuroprotection , dipeptide , hippocampal formation , nerve growth factor , pharmacology , alzheimer's disease , neuroscience , medicine , morris water navigation task , ischemia , chemistry , endocrinology , disease , psychology , biochemistry , receptor , peptide
Dipeptide mimetic of the nerve growth factor (NGF) loop 4, hexamethylenediamide bis-(N-monosuccinyl-glutamyl-lysine) (GK-2), was synthesized at the V.V. Zakusov Scientific Research Institute of Pharmacology of the Russian Academy of Medical Sciences. GK-2 exhibited in vitro neuroprotective activity at nanomolar concentrations, was efficient in animal models of the Parkinsons disease, ischemic and hemorrhagic stroke, and global cerebral ischemia at doses of 0.015 mg/kg (intraperitoneally) and 10 mg/kg (per os). The mnemotropic effects of subchronic intraperitoneal administration of GK-2 on rat models of the Alzheimers disease are described in this paper. Dipeptide GK-2 at a dose of 1 mg/kg is found to decrease the habituation deficit induced by the septo-hippocampal pathway transsection and, at a dose of 0.5 mg/kg, to significantly prevent spatial memory impairment in Morris water maze induced by intracerebral injection of streptozotocin. Thus, GK-2, an original dipeptide mimetic of NGF, acts on models of the Alzheimers disease upon systemic administration.