Investigation of the pharmacological activity of the tetrapeptide HAEЕ, zinc, and human serum albumin in a transgenic mouse model with tau protein overexpression (P301S)
Introduction: Neurodegenerative diseases affecting neurons represent a wide spectrum of pathological conditions. To slow the accumulation of pathological tau protein, therapeutic interventions such as a pharmaceutical composition consisting of the tetrapeptide HAEЕ, zinc, and albumin may be employed...
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| Language: | English |
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Belgorod National Research University
2025-03-01
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| Series: | Research Results in Pharmacology |
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| Online Access: | https://rrpharmacology.ru/index.php/journal/article/view/493 |
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| author | Veronika S. Shmigerova Yulia V. Stepenko Alexandra A. Kurbatova Nikita S. Zhunusov Nikita S. Lyapkalov Maria S. Sviridova Tatyana V. Avtina Arkadiy V. Nesterov Alexander A. Popov Natalia I. Nesterova Mariia Iu. Goltsova Tatiana G. Pokrovskaya |
| author_facet | Veronika S. Shmigerova Yulia V. Stepenko Alexandra A. Kurbatova Nikita S. Zhunusov Nikita S. Lyapkalov Maria S. Sviridova Tatyana V. Avtina Arkadiy V. Nesterov Alexander A. Popov Natalia I. Nesterova Mariia Iu. Goltsova Tatiana G. Pokrovskaya |
| author_sort | Veronika S. Shmigerova |
| collection | DOAJ |
| description | Introduction: Neurodegenerative diseases affecting neurons represent a wide spectrum of pathological conditions. To slow the accumulation of pathological tau protein, therapeutic interventions such as a pharmaceutical composition consisting of the tetrapeptide HAEЕ, zinc, and albumin may be employed. This composition possesses properties that can potentially slow disease progression.
Materials and Methods: The experiment was performed on 60 homozygous mice of both sexes from a transgenic line with the overexpression of human mutant tau protein (P301S) and on 20 mice from a wild-type C57Bl/6J background line. Control groups (C57Bl/6J – K and P301S – K+) received NaCl injection water (100 µL subcutaneously, once every 2 days); the experimental group (P301S) received HAEE-Zn-HSA (75 mg/kg, 150 µL subcutaneously, once every 2 days); and the comparison group (P301S) received piracetam (1.75 g/kg, 175 µL subcutaneously, once every 2 days). Behavioral activity was analyzed using tests at two time points, and the phenotypic presentation and lifespan were evaluated.
Results and Discussion: The P301S group of mice treated with HAEE-Zn-HSA at a dosage of 75 mg/kg showed positive behavioral activity in the following tests: Open Field, Novel Object Recognition, and Inverted grid test, indicating increased exploratory activity, and improved motor function and coordination in the mice of this group. Pharmacological intervention with HAEE-Zn-HSA in the experimental group of transgenic mice demonstrated positive results, as a statistically significant effect on lifespan and delayed onset of the phenotypic presentation of the disease was shown (24±2.14 weeks, p≤0.05).
Conclusion: The pharmaceutical composition HAEE-Zn-HSA at a dosage of 75 mg/kg, using a model of homozygous mice from a transgenic line with overexpression of human mutant tau protein P301S, demonstrated high levels of adaptive and exploratory activity and improved motor function. |
| format | Article |
| id | doaj-art-b11dd82bea3f4c76a9488a2dd0964097 |
| institution | OA Journals |
| issn | 2658-381X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Belgorod National Research University |
| record_format | Article |
| series | Research Results in Pharmacology |
| spelling | doaj-art-b11dd82bea3f4c76a9488a2dd09640972025-08-20T02:09:21ZengBelgorod National Research UniversityResearch Results in Pharmacology2658-381X2025-03-01111495710.18413/rrpharmacology.11.493Investigation of the pharmacological activity of the tetrapeptide HAEЕ, zinc, and human serum albumin in a transgenic mouse model with tau protein overexpression (P301S)Veronika S. Shmigerova0https://orcid.org/0000-0003-2941-0241Yulia V. Stepenko1https://orcid.org/0000-0002-7414-7326Alexandra A. Kurbatova2https://orcid.org/0009-0005-4658-507XNikita S. Zhunusov3https://orcid.org/0000-0002-1969-3615Nikita S. Lyapkalov4https://orcid.org/0009-0004-7208-5055Maria S. Sviridova5https://orcid.org/0009-0008-4078-0386Tatyana V. Avtina6https://orcid.org/0000-0003-0509-5996Arkadiy V. Nesterov7https://orcid.org/0000-0003-3822-4213Alexander A. Popov8https://orcid.org/0000-0002-5917-9813Natalia I. Nesterova9https://orcid.org/0000-0001-9927-5327Mariia Iu. Goltsova10https://orcid.org/0009-0007-5269-4154Tatiana G. Pokrovskaya11https://orcid.org/0000-0001-6802-5368Belgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversitBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityVoronezh State Medical University named after N. N. BurdenkoBelgorod Regional Bureau of Forensic Medical ExaminationPavlov First Saint Petersburg State Medical UniversityBelgorod State National Research UniversityIntroduction: Neurodegenerative diseases affecting neurons represent a wide spectrum of pathological conditions. To slow the accumulation of pathological tau protein, therapeutic interventions such as a pharmaceutical composition consisting of the tetrapeptide HAEЕ, zinc, and albumin may be employed. This composition possesses properties that can potentially slow disease progression. Materials and Methods: The experiment was performed on 60 homozygous mice of both sexes from a transgenic line with the overexpression of human mutant tau protein (P301S) and on 20 mice from a wild-type C57Bl/6J background line. Control groups (C57Bl/6J – K and P301S – K+) received NaCl injection water (100 µL subcutaneously, once every 2 days); the experimental group (P301S) received HAEE-Zn-HSA (75 mg/kg, 150 µL subcutaneously, once every 2 days); and the comparison group (P301S) received piracetam (1.75 g/kg, 175 µL subcutaneously, once every 2 days). Behavioral activity was analyzed using tests at two time points, and the phenotypic presentation and lifespan were evaluated. Results and Discussion: The P301S group of mice treated with HAEE-Zn-HSA at a dosage of 75 mg/kg showed positive behavioral activity in the following tests: Open Field, Novel Object Recognition, and Inverted grid test, indicating increased exploratory activity, and improved motor function and coordination in the mice of this group. Pharmacological intervention with HAEE-Zn-HSA in the experimental group of transgenic mice demonstrated positive results, as a statistically significant effect on lifespan and delayed onset of the phenotypic presentation of the disease was shown (24±2.14 weeks, p≤0.05). Conclusion: The pharmaceutical composition HAEE-Zn-HSA at a dosage of 75 mg/kg, using a model of homozygous mice from a transgenic line with overexpression of human mutant tau protein P301S, demonstrated high levels of adaptive and exploratory activity and improved motor function.https://rrpharmacology.ru/index.php/journal/article/view/493tauopathytau proteinbehavioral activitytransgenic micehaee-zn-hsa complex pharmaceutical composition |
| spellingShingle | Veronika S. Shmigerova Yulia V. Stepenko Alexandra A. Kurbatova Nikita S. Zhunusov Nikita S. Lyapkalov Maria S. Sviridova Tatyana V. Avtina Arkadiy V. Nesterov Alexander A. Popov Natalia I. Nesterova Mariia Iu. Goltsova Tatiana G. Pokrovskaya Investigation of the pharmacological activity of the tetrapeptide HAEЕ, zinc, and human serum albumin in a transgenic mouse model with tau protein overexpression (P301S) Research Results in Pharmacology tauopathy tau protein behavioral activity transgenic mice haee-zn-hsa complex pharmaceutical composition |
| title | Investigation of the pharmacological activity of the tetrapeptide HAEЕ, zinc, and human serum albumin in a transgenic mouse model with tau protein overexpression (P301S) |
| title_full | Investigation of the pharmacological activity of the tetrapeptide HAEЕ, zinc, and human serum albumin in a transgenic mouse model with tau protein overexpression (P301S) |
| title_fullStr | Investigation of the pharmacological activity of the tetrapeptide HAEЕ, zinc, and human serum albumin in a transgenic mouse model with tau protein overexpression (P301S) |
| title_full_unstemmed | Investigation of the pharmacological activity of the tetrapeptide HAEЕ, zinc, and human serum albumin in a transgenic mouse model with tau protein overexpression (P301S) |
| title_short | Investigation of the pharmacological activity of the tetrapeptide HAEЕ, zinc, and human serum albumin in a transgenic mouse model with tau protein overexpression (P301S) |
| title_sort | investigation of the pharmacological activity of the tetrapeptide haeе zinc and human serum albumin in a transgenic mouse model with tau protein overexpression p301s |
| topic | tauopathy tau protein behavioral activity transgenic mice haee-zn-hsa complex pharmaceutical composition |
| url | https://rrpharmacology.ru/index.php/journal/article/view/493 |
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