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

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.

Author information

1
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia apbogachouk@gmail.com.
2
Federal Medical Research Centre of Psychiatry and Narcology, Moscow, Russia.
3
Anokhin Institute of Normal Physiology, Moscow, Russia.
4
Institute of Molecular Genetics of RAS, Moscow, Russia.
5
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Pushchino, Russia.
6
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.

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.

KEYWORDS:

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

PMID:
26628555
DOI:
10.1177/0269881115616393
[Indexed for MEDLINE]

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