Comparative study of the neuroprotective and nootropic activities of the carboxylate and amide forms of the HLDF-6 peptide in animal models of Alzheimer's disease.

Abstract

A comparative study of the neuroprotective and nootropic activities of two pharmaceutical substances, the HLDF-6 peptide (HLDF-6-OH) and its amide form (HLDF-6-NH2), was conducted. The study was performed in male rats using two models of a neurodegenerative disorder. Cognitive deficit in rats was induced by injection of the beta-amyloid fragment 25-35 (βA 25-35) into the giant-cell nucleus basalis of Meynert or by coinjection of βA 25-35 and ibotenic acid into the hippocampus. To evaluate cognitive functions in animals, three tests were used: the novel object recognition test, the conditioned passive avoidance task and the Morris maze. Comparative analysis of the data demonstrated that the neuroprotective activity of HLDF-6-NH2, evaluated by improvement of cognitive functions in animals, surpassed that of the native HLDF-6-OH peptide. The greater cognitive/ behavioral effects can be attributed to improved kinetic properties of the amide form of the peptide, such as the character of biodegradation and the half-life time. The effects of HLDF-6-NH2 are comparable to, or exceed, those of the reference compounds. Importantly, HLDF-6-NH2 exerts its effects at much lower doses than the reference compounds.

• Authors: Anna P Bogachouk, Zinaida I Storozheva, Olga A Solovjeva, Vyacheslav V Sherstnev, Yury A Zolotarev, Vyacheslav N Azev, Igor L Rodionov, Elena A Surina, Valery M Lipkin
• Journal: Journal of psychopharmacology (Oxford, England) (J Psychopharmacol) Vol. 30 Issue 1 Pg. 78-92 (Jan 2016) ISSN: 1461-7285 [Electronic] United States
• PMID: 26628555 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2015.

Chemical References

• Amides
• Carboxylic Acids
• Neuroprotective Agents
• Nootropic Agents
• Oligopeptides
• threonyl-glycyl-glutamyl-asparaginyl-histidylarginine

Topics

• Alzheimer Disease (drug therapy, physiopathology)
• Amides (chemistry)
• Animals
• Avoidance Learning (drug effects)
• Carboxylic Acids (chemistry)
• Cognition Disorders (drug therapy, physiopathology)
• Disease Models, Animal
• Male
• Maze Learning (drug effects)
• Neuroprotective Agents (chemistry, pharmacokinetics, pharmacology)
• Nootropic Agents (chemistry, pharmacokinetics, pharmacology)
• Oligopeptides (chemistry, pharmacokinetics, pharmacology)
• Rats
• Rats, Wistar