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

J Psychopharmacol. 2016 Jan;30(1):78-92. doi: 10.1177/0269881115616393. Epub 2015 Dec 1.


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.

Keywords: Alzheimer’s disease (AD); HLDF-6 peptide; Human leukemia differentiation factor (HDLF); beta-amyloid fragment 25–35 (βA 25–35); neuroprotection; nootropic activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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


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