The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model.
The effects of the novel proline-containing nootropic and neuroprotective dipeptide, noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were investigated in NMRI mice following olfactory bulbectomy. We have shown previously that these animals developed Alzheimer's disease (AD)-like behaviour, morphology and biochemistry including impairment of spatial memory, regional neuronal degeneration and elevated Abeta peptide brain levels. In the current investigation, spatial memory was assessed using the Morris water maze and serum antibodies to in vitro morphologically characterized amyloid structures of both Abeta((25-35)) peptide and equine lysozyme, as well as to neurotrophic glial factor S100b, were analyzed by enzyme-linked immunosorbent assay (ELISA). Noopept (administered at a dose of 0.01 mg/kg for a period of 21 days and during a further 5 days training) restored spatial memory and increased serum antibody levels to oligomers of Abeta((25-35)) peptide but not to equine lysozyme amyloid or S100b protein in bulbectomized animals. The positive immunotropic effect of noopept to Abeta((25-35)) peptide prefibrillar aggregates was more marked in sham-operated compared to the bulbectomized subjects which were characterized by an overall suppression of immunoreactivity. Enhancement of the immune response to Abeta((25-35)) peptide prefibrils caused by noopept may attenuate the neurotoxic consequences of amyloid fibrillization and also be associated with an improvement in spatial memory in bulbectomized mice. These actions of noopept, combined with its previously reported neuroprotective and cholinomimetic properties, suggests that this dipeptide may well be useful for improving cognitive deficits induced by neurodegenerative diseases.
Ostrovskaya
Rita U
RU
V. V. Zakusov State Institute of Pharmacology, Moscow, Russia.
Gruden
Marina A
MA
Bobkova
Natalya A
NA
Sewell
Robert D E
RD
Gudasheva
Tatyana A
TA
Samokhin
Alexander N
AN
Seredinin
Sergey B
SB
Noppe
Wim
W
Sherstnev
Vladimir V
VV
Morozova-Roche
Ludmilla A
LA
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001522:Behavior, Animal / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018625:Microscopy, Atomic Force; D009113:Muramidase / Q000276:immunology; D009414:Nerve Growth Factors / Q000276:immunology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018697:Nootropic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009830:Olfactory Bulb / Q000601:surgery; D010446:Peptide Fragments / Q000276:immunology*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000276:immunology; D013028:Space Perception / Q000187:drug effects*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D004151:Dipeptides; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010446:Peptide Fragments; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse; C074636:amyloid beta-protein (25-35); C103871:ethyl phenylacetyl-Pro-Gly; D009113:Muramidase