Original Nerve Growth Factor Mimetic Dipeptide GK-2 Restores Impaired Cognitive Functions in Rat Models of Alzheimer’s Disease

Author:

Povarnina P. Yu.,Vorontsova O. N.,Gudasheva T. A.,Ostrovskaya R. U.,Seredenin S. B.

Abstract

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.

Publisher

Acta Naturae Ltd

Subject

Molecular Biology,Molecular Medicine,Biochemistry,Biotechnology

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