The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer’s Disease - Research Article

Sep 28, 2026

Alzheimer’s disease remains one of the most prevalent neurodegenerative disorders, and safe, effective remedies that halt or significantly slow pathology are still lacking. This study evaluated the neuroprotective peptide Semax and its derivative for their impact on behavior and amyloidosis development in transgenic APPswe/PS1dE9/Blg mice modeling Alzheimer’s disease. Behavioral testing (open field, novel object recognition, Barnes maze) showed improved cognitive performance, while histology indicated fewer amyloid inclusions in cortex and hippocampus, supporting Semax’s therapeutic potential.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Keywords and Abbreviations

Introduction

Alzheimer’s disease overview and treatment challenges

Role of animal models in AD drug research

Semax and rationale for studying its derivative

RESEARCH ARTICLES The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer’s Disease A. I. Radchenko 1 , E. V. Kuzubova 1 , A. A. Apostol 1 , V. A. Mitkevich2* , L. A. Andreeva3 , S. A. Limborska3 , Yu. V. Stepenko 1 , V. S. Shmigerova 1 , A. V. Solin 1 , M. V. Korokin 1 , M. V. Pokrovskii 1 , N. F. Myasoedov3 , A. A. Makarov2 1Belgorod State National Research University, Belgorod, 308015 Russia 2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia 3National Research Center “Kurchatov Institute”, Moscow, 123182 Russia * [E-mail: mitkevich@gmail.com](E-mail: mitkevich@gmail.com) Received September 03, 2025; in final form, September 29, 2025 DOI: 10.32607/actanaturae.27808 Copyright © 2025 National Research University Higher School of Economics. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Alzheimer’s disease, first described over a century ago, is currently among the most common neurodegenerative diseases whose significance is increasingly growing with the aging of populations. Throughout the entire period of its study, no remedies have been found that would be effective in treating – or at least significantly slowing – the pathological process, while being sufficiently safe. In this regard, significant attention is paid to the development and application of natural peptide drugs lacking side effects. The present study assessed the effect of the known neuroprotective peptide Semax and its derivative on the behavioral characteristics and development of amyloidosis in transgenic APPswe/PS1dE9/Blg mice acting asa model of Alzheimer’s disease. The open field, novel object recognition, and Barnes maze tests demonstrated that both Semax and its derivative improved cognitive functions in mice. Histological examination showed that these peptides reduced the number of amyloid inclusions in the cortex and hippocampus of the animals’brains. These findings demonstrate the high potential of Semax and its derivatives when used to develop therapeutic and corrective strategies for Alzheimer’s disease. KEYWORDS Alzheimer’s disease, peptide drug, behavioral testing, histological analysis, amyloidosis. ABBREVIATIONSAD – Alzheimer’s disease; Aβ – beta-amyloid peptide; APP/PS1 – APPswe/PS1dE9 transgenic mice; ACTH(4–7)– adrenocorticotropic hormone fragment (4–7); Heptapeptide – Met-Glu-Asp-Arg-Pro-GlyPro peptide; WT – Wild type, C57BL/6 mice. INTRODUCTION Alzheimer’s disease (AD) is currently among the most prevalent neurodegenerative disorders in the elderly and senile populations [1–4]. The progressive form of AD can be caused by cerebral disorders, intoxication, infection, and defects in the pulmonary and circulatory systems, leading to reduced oxygen supply to the brain, by nutrient and vitamin B12 deficiency, as well as by tumors [5–8]. AD is the most common type of dementia and can be defined as a slowly progressive neurodegenerative disease characterized by the formation of senile plaques and neurofibrillary tangles via the accumulation of beta-amyloid peptide (Aβ) and tau protein within the most affected brain regions: the medial temporal lobe and neocortical structures [9–11]. The number of pharmaceuticals used to treat Alzheimer’s disease remains limited [12, 13] . Therefore, there is an ongoing need for novel compounds that would mitigate the cognitive impairment caused by disease progression [14, 15]. Animal models of AD play a crucial role in this research, as they make possible a detailed investigation of drug effects on key characteristics of the disease. The APPswe/PS1dE9/Blg (APP/PS1) transgenic mouse line, commonly used to study the mechanisms of AD and methods to correct them, is such a model [16] . Signific

FAQs

What was the goal of testing Semax and its derivative in this study?

To assess how Semax and its derivative affect behavioral characteristics and the development of amyloidosis in a transgenic mouse model of Alzheimer’s disease.

Which behavioral tests were used to evaluate cognitive functions?

The study used the open field test, novel object recognition, and Barnes maze to assess cognitive performance in mice.

What did histological examination show after treatment?

Histological analysis showed that both peptides reduced the number of amyloid inclusions in the cortex and hippocampus of the animals’ brains.

Sep 28, 2026

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