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

Abstract

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.

Original nootropic drug Noopept prevents memory deficit in rats with muscarinic and nicotinic receptor blockade

“…Our results are consistent with published data that Noopept normalizes spatial orientation and memory in the Morris water maze during scopolamine-induced amnesia [1] and olfactory bulbectomy (model of Alzheimer's disease) [13]. Noopept exhibits cholinepositive activity and produces a strong nootropic and neuroprotective effect on various models of brain injury [5,13].…”

“…Noopept exhibits cholinepositive activity and produces a strong nootropic and neuroprotective effect on various models of brain injury [5,13]. Hence, Noopept holds much promise for the therapy of neurodegenerative diseases.…”

Methylthioninium chloride reverses cognitive deficits induced by scopolamine: comparison with rivastigmine

“…Selective comparisons between mouse strains show that NMRI mice have lower levels of M1 receptors relative to C57BL/6 or Balb/C strains (Yilmazer-Hanke et al 2003) and the expression levels in hippocampus (Lamberty et al 1992) and cortex (Eriksson and Fredriksson 1991) correlate negatively with the overall behavioural activity measured in the open field and positively with spatial performance. Therefore, scopolamine-induced reductions of cholinergic activity in NMRI mice is a valid amnesia model, with features reminiscent of AD (Ostrovskaya et al 2007). …”

Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by β-amyloid25–35 injection into Meynert basal nuclei of rats)

“…A pronounced antiinflammatory effect of noopept was detected [1]. Noopept stimulation of production of antibodies to Aβ (25-35) (which can also lead to attenuation of its neurotoxic effect), detected on the model of olfactory bulbectomy [12], is also worthy of note within the framework of these studies.…”

“…Comparison of the structure of standard nootrope (piracetam) with the structure of N-terminal fragment of the main fragment of vasopressin ("memory peptide") led to creation of a series of acylproline-containing dipeptides [14], from which N-phenylacetyl-L-prolylglycine ethyl ether (GVC-111; Noopept) was selected. Detailed studies detected a complex of nootropic and neuroprotective characteristics in noopept [2], manifesting, on AD models, for example, under conditions of chronic blockade of cholinergic receptors [3] and olfactory bulbectomy [12].…”