The multiple T-maze in vivo testing of the neuroprotective effect of humanin analogues.
Humanin (HN) and its analogues have been shown to protect cells against death induced by various Alzheimer's disease (AD) genes and amyloid-beta-peptides in vitro; the analogues [Gly(14)]-HN and colivelin have also been shown to be potent in reversing learning and memory impairment induced by scopolamine or quinuclidinyl benzilate (QNB) in mice or rats in vivo using the Y-maze or multiple T-maze tests. This paper describes the activity of new peptides of the HN family, after i.p. administration, on QNB-induced impairment of spatial memory in the multiple T-maze test in rats. The following peptides have been studied: HN analogues truncated either on the C- or N-terminus, or analogues having a tert-Leu in place of Leu in the central part of the molecule, the active HN core PAGASRLLLLTGEIDLP (RG-PAGA) and its analogues having three or five leucines instead of four, and finally the recently described hybrid peptide colivelin (i.e. a peptide having the activity-dependent neurotrophic factor SALLRSIPA attached to the N-terminus of the active RG-PAGA) and its des-Leu- and plus-Leu-analogues. While the truncated analogues and most of the tert-Leu containing analogues were devoid of activity, the analogues of the RG-PAGA were active, i.e. they reversed the impairment of spatial memory irrespective of the number of Leu present in their sequence. The highest activity was shown by colivelin and its des-Leu-analogue. These results demonstrate the potential of HN analogues in the modulation of the cholinergic system, which plays an important role in the cognitive deficits associated with AD and other neurodegenerative diseases.
Kunesová
Gabriela
G
Department of Toxicology, University of Defense, Trebesská 1575, 500 01 Hradec Králové, Czech Republic.
Hlavácek
Jan
J
Patocka
Jirí
J
Evangelou
Alexandra
A
Zikos
Christos
C
Benaki
Dimitra
D
Paravatou-Petsotas
Maria
M
Pelecanou
Maria
M
Livaniou
Evangelia
E
Slaninova
Jirina
J
D000818:Animals; D047908:Intracellular Signaling Peptides and Proteins / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009949:Orientation / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D011813:Quinuclidinyl Benzilate; D051381:Rats; D017208:Rats, Wistar
D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D010455:Peptides; C427211:humanin; D011813:Quinuclidinyl Benzilate