The Neuroprotective Effect of the HLDF-6 Peptides in the Experimental Model of Preclinical Stage of Parkinson's Disease

39 Pages Posted: 19 Jul 2022

See all articles by Yurii A. Zolotarev

Yurii A. Zolotarev

National Research Center Kurchatov Institute

Stanislav I. Shram

National Research Center Kurchatov Institute

Aleksandr K. Dadayan

National Research Center Kurchatov Institute

Oleg V. Dolotov

Lomonosov Moscow State University, Faculty of Biology, Russia; National Research Center Kurchatov Institute

Dmitriy D. Markov

National Research Center Kurchatov Institute

Igor Yu. Nagaev

National Research Center Kurchatov Institute

Vladimir S. Kudrin

Zakusov Research Institute of Pharmacology

Viktor B. Narkevich

Zakusov Research Institute of Pharmacology

Oleg Yu. Sokolov

Mental Health Research Center

Natalya V. Kost

Mental Health Research Center

Abstract

The mechanisms of the neuroprotective action of the hexapeptides HLDF-6 and HLDF-6-H, derivatives of the fragment 41-46 of the Human Leukemia Differentiation Factor, were determined in an experimental MPTP model of Parkinson's disease (PD) in C57Bl/6 mice (two intraperitoneal injections of MPTP-HCl, 18 mg/kg, with an interval of 2 hours). For the analysis of motor disturbances in the preclinical stage of PD, the "Horizontal grid" test was used. It was found that chronic administration of peptides (intranasally, 3 weeks, 300 μg/kg/day) restored the level of dopamine and its turnover in the striatum, increased the level of serum estradiol and led to a significant improvement in motor dysfunctions. In addition, the peptides normalized the mRNA levels of the neurotrophin BDNF and inflammatory mediators TGFβ1, IL1β and IFNγ in the brain. The findings provide evidence that the HLDF-6 peptides have a therapeutic potential to treat PD. The neuroprotective mechanism may involve the normalizing estradiol levels and expression of key factors of neurotrophic support and neuroinflammation

Note:

Funding Information: This study was partially supported by the Program for Basic Research of the Presidium of the Russian Academy of Sciences, project no. 01201353020 (“Structure-Functional Investigation of Endogenous Peptides Is a Basis of the Creation of Novel Pharmacologically Important Medicines).

Declaration of Interests: The authors declare no conflicts of interest.

Ethical Approval Statement: All experimental procedures were carried out following: National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23, revised 1996); the UK Animals Scientific Procedures Act 1986 and associated guidelines; the European Communities Council Directive of 24 November 1986 (86/609/EEC) for care and use of laboratory animals. They were also approved by the Animal Care and Use Committee of the Institute of Molecular Genetics of RAS, Moscow, Russia.

Keywords: Models of Parkinson's disease, peptide HLDF-6, neuroprotectors, neurotrophic factors, test "Horizontal grid"

Suggested Citation

Zolotarev, Yurii A. and Shram, Stanislav I. and Dadayan, Aleksandr K. and Dolotov, Oleg V. and Markov, Dmitriy D. and Nagaev, Igor Yu. and Kudrin, Vladimir S. and Narkevich, Viktor B. and Sokolov, Oleg Yu. and Kost, Natalya V., The Neuroprotective Effect of the HLDF-6 Peptides in the Experimental Model of Preclinical Stage of Parkinson's Disease. Available at SSRN: https://ssrn.com/abstract=4163318 or http://dx.doi.org/10.2139/ssrn.4163318

Yurii A. Zolotarev (Contact Author)

National Research Center Kurchatov Institute ( email )

Stanislav I. Shram

National Research Center Kurchatov Institute ( email )

Aleksandr K. Dadayan

National Research Center Kurchatov Institute ( email )

Oleg V. Dolotov

Lomonosov Moscow State University, Faculty of Biology, Russia

Leninskie Gory
Moscow, 119234
Russia

National Research Center Kurchatov Institute ( email )

Dmitriy D. Markov

National Research Center Kurchatov Institute ( email )

Igor Yu. Nagaev

National Research Center Kurchatov Institute ( email )

Vladimir S. Kudrin

Zakusov Research Institute of Pharmacology ( email )

Viktor B. Narkevich

Zakusov Research Institute of Pharmacology ( email )

Oleg Yu. Sokolov

Mental Health Research Center ( email )

Natalya V. Kost

Mental Health Research Center ( email )

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