[Neuroprotective effect of the hexapeptide HLDF-6 on neurons of rat hippocampus on the model of Alzheimer's disease in vivo and in vitro].
The neuroprotective effect of Thr-Gly-Glu-Asn-His-Arg hexapeptide (HLDF-6), a biologically active fragment of the differentiation factor of human leukemia cells (HLDF), was demonstrated on models of Alzheimer's disease in vivo and in vitro. The syndromes of this pathology were induced in male rats by administration of the peptide corresponding to the 25-35 sequence of beta-amyloid peptide (25-35) and ibotenic acid into the hippocampus. HLDF-6 prevented loss of long-term memory and decrease in the orientation-investigation activity of these animals and significantly decreased the number of pyknotic neurons in the CA1 area of the hippocampus. This peptide also exerts a protective effect in vitro on the primary cultures of neurons of the hippocampus and cerebellum of rats under conditions of the beta-amyloid toxicity. An increase in the dihydrotestosterone (DHT) content was demonstrated in the blood plasma of rats with the syndrome of Alzheimer's disease and in the medium of the culture of hippocampus neurons in the presence of the Abeta(25-35) peptide. HLDF-6 inhibited this increase in both cases. A probable mechanism of the neuroprotective effect of HLDF-6 was suggested as being connected to its possible effect on both the biosynthesis and the metabolism of sex steroid hormones.
Kostanian
I A
IA
Zhokhov
S S
SS
Storozheva
Z I
ZI
Proshin
A T
AT
Surina
E A
EA
Babichenko
I I
II
Sherstnev
V V
VV
Lipkin
V M
VM
D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D004967:Estrogens / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007051:Ibotenic Acid / Q000633:toxicity; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D016229:Amyloid beta-Peptides; D004967:Estrogens; D018696:Neuroprotective Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D013256:Steroids; C074636:amyloid beta-protein (25-35); C513648:threonyl-glycyl-glutamyl-asparaginyl-histidylarginine; D007051:Ibotenic Acid; D013739:Testosterone