title: Original Nerve Growth Factor Mimetic Dipeptide GK-2 Restores Impaired Cognitive Functions in Rat Models of Alzheimer's Disease.
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 Parkinson's disease, ischemic and hemorrhagic stroke, and global cerebral ischemia at doses of 0.01-5 mg/kg (intraperitoneally) and 10 mg/kg (per os). The mnemotropic effects of subchronic intraperitoneal administration of GK-2 on rat models of the Alzheimer's 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 Alzheimer's disease upon systemic administration.
authors.affiliation: Zakusov Institute of Pharmacology, RAMS, Baltiyskaya Str., 8, Moscow, Russia, 125315.
authors.forename: P Yu
authors.initials: PY
authors.lastname: Povarnina
authors.forename: O N
authors.initials: ON
authors.lastname: Vorontsova
authors.forename: T A
authors.initials: TA
authors.lastname: Gudasheva
authors.forename: R U
authors.initials: RU
authors.lastname: Ostrovskaya
authors.forename: S B
authors.initials: SB
authors.lastname: Seredenin
keywords: GK-2; Morris water maze; habituation; low molecular mimetic of NGF; septo-hippocampal transsection; streptozotocin model of Alzheimer’s disease