HAEE tetrapeptide as a promising neuroprotector: comparison with Piracetam in an experimental model of Alzheimer's disease

Abstract

Introduction: During the experiment, the effectiveness of tetrapeptide HAEE and the comparison drug Piracetam in correcting neurodegenerative disorders in Alzheimer's disease was investigated in a model of transgenic mice.

Materials and Methods: transgenic mice of the APPswe/PS1dE9 (APP/PS1) line were used in the study. The animals were injected with HAEE and Piracetam, after which behavioral tests were performed (“Open Field”, “Light‑Dark Chamber”, “Novel Object Recognition”, “Barnes Maze”). Additionally, gene expression was analyzed using real‑time PCR. The histological study included staining of brain sections with Congo red, followed by counting amyloid plaques in the cortex and hippocampus.

Results and Discussion: The administration of HAEE and Piracetam led to an improvement in cognitive performance, with both groups demonstrating memory recovery to the level of intact controls. Histological analysis showed an increase in the number of amyloid plaques in the positive control animals and a reduction in the therapeutic groups by an average of 40%. Gene expression analysis showed that HAEE and Piracetam modulate key molecular pathways associated with neuroplasticity, inflammation, and cellular survival. Changes in the expression of the Stat3, mTor, Vegfa, and Casp3 genes have been observed, reflecting the activation of compensatory neuroprotective mechanisms, as well as the relative stabilization of the pro‑inflammatory markers Il‑6 and Tnf‑a.

Conclusion: HAEE tetrapeptide at a dosage of 50 mg per 1 kg and Piracetam at a dosage of 200 mg/kg have a comprehensive positive effect on cognitive functions, molecular and morphological parameters in Alzheimer’s disease. The results obtained in the animal model confirm its high potential as a promising neuroprotective agent, comparable to or superior to classical nootropic drugs.

Graphical Abstract