title: 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.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia apbogachouk@gmail.com.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Bogachouk
authors.affiliation: Federal Medical Research Centre of Psychiatry and Narcology, Moscow, Russia.
authors.forename: Zinaida I
authors.initials: ZI
authors.lastname: Storozheva
authors.affiliation: Anokhin Institute of Normal Physiology, Moscow, Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Solovjeva
authors.affiliation: Anokhin Institute of Normal Physiology, Moscow, Russia.
authors.forename: Vyacheslav V
authors.initials: VV
authors.lastname: Sherstnev
authors.affiliation: Institute of Molecular Genetics of RAS, Moscow, Russia.
authors.forename: Yury A
authors.initials: YA
authors.lastname: Zolotarev
authors.affiliation: Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Pushchino, Russia.
authors.forename: Vyacheslav N
authors.initials: VN
authors.lastname: Azev
authors.affiliation: Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Pushchino, Russia.
authors.forename: Igor L
authors.initials: IL
authors.lastname: Rodionov
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Surina
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.
authors.forename: Valery M
authors.initials: VM
authors.lastname: Lipkin
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000577:Amides / Q000737:chemistry; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002264:Carboxylic Acids / Q000737:chemistry; D003072:Cognition Disorders / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018697:Nootropic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000577:Amides; D002264:Carboxylic Acids; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D009842:Oligopeptides; C513648:threonyl-glycyl-glutamyl-asparaginyl-histidylarginine
keywords: Alzheimer’s disease (AD); HLDF-6 peptide; Human leukemia differentiation factor (HDLF); beta-amyloid fragment 25–35 (βA 25–35); neuroprotection; nootropic activity