This Article Full Text (PDF) All Versions of this Article: 0269881106071335v1 21/6/611    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ostrovskaya, R. U. Articles by Morozova-Roche, L. A. Search for Related Content PubMed PubMed Citation Articles by Ostrovskaya, R. U. Articles by Morozova-Roche, L. A. Social Bookmarking                   What's this?

The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model

V. V. Zakusov State Institute of Pharmacology, Moscow, Russia

Marina A. Gruden

P. K. Anokhin State Institute of Normal Physiology, Moscow, Russia

Natalya A. Bobkova

Institute of Cell Biophysics, Moscow Region, Puschino, Russia

Robert D. E. Sewell

Welsh School of Pharmacy, Cardiff University, Cardiff, UK, sewell{at}cardiff.ac.uk

Tatyana A. Gudasheva

V. V. Zakusov State Institute of Pharmacology, Moscow, Russia

Alexander N. Samokhin

Institute of Cell Biophysics, Moscow Region, Puschino, Russia

Sergey B. Seredinin

Zakusov State Institute of Pharmacology, Moscow, Russia

Wim Noppe

Interdisciplinary Research Center, Campus Kortrijk, KU Keuven, Kortrijk, Belgium

Vladimir V. Sherstnev

P. K. Anokhin State Institute of Normal Physiology, Moscow, Russia

Ludmilla A. Morozova-Roche

Department of Medical Biochemistry and Biophysics, UmeÅ University, UmeÅ, Sweden

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 Aß 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 Aß_(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 Aß_(25—35) peptide but not to equine lysozyme amyloid or S100b protein in bulbectomized animals. The positive immunotropic effect of noopept to Aß_(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 Aß_(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 it's previously reported neuroprotective and cholinomimetic properties, suggests that this dipeptide may well be useful for improving cognitive deficits induced by neurodegenerative diseases.

Key Words: noopept (GVS-111) • memory improvement • olfactory bulbectomy • Alzheimer's disease • antibodies • Aß(25—35) peptide • amyloid

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?