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THE NOOTROPIC EFFECT OF A DIPEPTIDE MIMETIC OF NGF IN AN EXPERIMENTAL MODEL OF ALZHEIMER'S DISEASE

DOI: https://doi.org/10.29296/25877313-2023-11-10
Issue: 
11
Year: 
2023

A.A. Volkova
Post-graduate Student, Department of Human and Animal Physiology, Faculty of Biology,
M.V. Lomonosov Moscow State University;
Junior Researcher, Department of Medicinal Chemistry,
FSBI «V.V. Zakusov Institute of Pharmacology» (Moscow, Russia)
E-mail: volk3012@gmail.com
P.Yu. Povarnina
Ph.D. (Biol.), Senior Researcher, Department of Medicinal Chemistry,
FSBI «V.V. Zakusov Institute of Pharmacology» (Moscow, Russia)
E-mail: povarnina@gmail.com
T.A. Gudasheva
Dr.Sc. (Biol.), Professor, Corresponding Member of the Russian Academy of Sciences,
Head of the Department of Medicinal Chemistry,
FSBI «V.V. Zakusov Institute of Pharmacology» (Moscow, Russia)
E-mail: gudasheva@academpharm.ru

Relevance. The role of nerve growth factor (NGF) deficiency in the pathogenesis of Alzheimer's disease (AD) is well-known. The clinical application of full-size neurotrophin is limited due to its low bioavailability and the risk of adverse effects. At the V.V. Zakusov Institute of Pharmacology, a dimeric di-peptide mimetic of the 4th loop of NGF, compound GK-2 (hexamethylenediamide bis-(N-monosuccinyl-L-glutamyl-L-lysine), was created. It selectively activates specific TrkA receptors and possesses neuroprotective and neuroregenerative properties. Additionally, GK-2 lacks the main side effects of NGF, namely hyperalgesia and weight loss. The aim of the current study was to investigate the influence of GK-2 on rat memory under the conditions of the scopolamine-induced model of AD. Material and Methods. Scopolamine was administered intraperitoneally to rats at a dose of 2 mg/kg for 32 days. Simultaneously with scopolamine, animals were intraperitoneally injected with GK-2 at doses of 0.5 and 1 mg/kg. Following the administration of the compounds, a novel object recogni-tion test was conducted to assess both short-term and long-term memory. Results. Rats receiving scopolamine exhibited a statistically significant decline in long-term memory. The dipeptide GK-2 at a dose of 1 mg/kg com-pletely counteracted the development of this impairment. Conclusion. The dipeptide mimetic of nerve growth factor, GK-2, shows promise for further investigation as a potential therapeutic agent for the treatment of AD.
Keywords: 
nerve growth factor
NGF
dipeptide mimetic
GK-2
Alzheimer's disease
scopolamine
memory.
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