Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biomed Sci. 2014 Aug 6;21:74. doi: 10.1186/s12929-014-0074-2.

Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation.

Author information

1
Zakusov Institute of Pharmacology RAS, Baltiyskaya 8, 125315, Moscow, Russia. rita.ostrovskaya@gmail.com.
2
Institute of Biochemistry and Genetics Ufa Scientific Centre RAS, Prospect Oktyabrya, 71, 450054, Ufa, Russia. juvv73@gmail.com.
3
Institute of Biochemistry and Genetics Ufa Scientific Centre RAS, Prospect Oktyabrya, 71, 450054, Ufa, Russia. miph@anrb.ru.
4
Zakusov Institute of Pharmacology RAS, Baltiyskaya 8, 125315, Moscow, Russia. tata-sosnovka@mail.ru.
5
Institute of Biochemistry and Genetics Ufa Scientific Centre RAS, Prospect Oktyabrya, 71, 450054, Ufa, Russia. vakhitov@anrb.ru.
6
Zakusov Institute of Pharmacology RAS, Baltiyskaya 8, 125315, Moscow, Russia. niipharm@mail.ru.

Abstract

BACKGROUND:

Noopept (N-phenyl-acetyl-L-prolylglycine ethyl ester) was constructed as a dipeptide analog of the standard cognition enhancer, piracetam. Our previous experiments have demonstrated the cognition restoring effect of noopept in several animal models of Alzheimer disease (AD). Noopept was also shown to prevent ionic disbalance, excitotoxicity, free radicals and pro-inflammatory cytokines accumulation, and neurotrophine deficit typical for different kinds of brain damages, including AD. In this study, we investigated the neuroprotective action of noopept on cellular model of AD, Aβ 25-35-induced toxicity in PC12 cells and revealed the underlying mechanisms.

RESULTS:

The neuroprotective effect of noopept (added to the medium at 10 μM concentration, 72 hours before Аβ 25-35) was studied on Аβ 25-35-induced injury (5 μM for 24 h) in PC12 cells. The ability of drug to protect the impairments of cell viability, calcium homeostasis, ROS level, mitochondrial function, tau phosphorylation and neurite outgrowth caused by Аβ 25-35 were evaluated. Following the exposure of PC12 cells to Аβ 25-35 an increase of the level of ROS, intracellular calcium, and tau phosphorylation at Ser396 were observed; these changes were accompanied by a decrease in cell viability and an increase of apoptosis. Noopept treatment before the amyloid-beta exposure improved PC12 cells viability, reduced the number of early and late apoptotic cells, the levels of intracellular reactive oxygen species and calcium and enhanced the mitochondrial membrane potential. In addition, pretreatment of PC12 cell with noopept significantly attenuated tau hyperphosphorylation at Ser396 and ameliorated the alterations of neurite outgrowth evoked by Аβ25-35.

CONCLUSIONS:

Taken together, these data provide evidence that novel cognitive enhancer noopept protects PC12 cell against deleterious actions of Aβ through inhibiting the oxidative damage and calcium overload as well as suppressing the mitochondrial apoptotic pathway. Moreover, neuroprotective properties of noopept likely include its ability to decrease tau phosphorylation and to restore the altered morphology of PC12 cells. Therefore, this nootropic dipeptide is able to positively affect not only common pathogenic pathways but also disease-specific mechanisms underlying Aβ-related pathology.

PMID:
25096780
PMCID:
PMC4422191
DOI:
10.1186/s12929-014-0074-2
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Support Center