Investigation of the pharmacological activity of the tetrapeptide HAEЕ, zinc, and human serum albumin in a transgenic mouse model with tau protein overexpression (P301S)

Abstract

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.

Graphical Abstract