NMDA-mechanisms in involvement in the cognitive enhancing effect of novel substituted acylprolyl-dipeptide

Ostrovskaya, R. U.; Firova, F. A.; Trofimov, S. S.; Кравченко, Елена; Gudasheva, T. A.

doi:10.1016/1043-6618(95)87614-6

Cited by 2 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of Noopept action has been studied since its synthesis. It has been established that the drug increases the expression of NGF and BDNF in the hippocampus [ 8 ], exhibits choline-positive properties at behavioral and neuronal levels [ 9 ], reduces oxidative stress and enhances the activity of antioxidant systems [ 7 , 10 ], and represses kinases pSAPK/JNK and pERK1 induced by stress [ 11 ]. However, the study of the primary interactions of Noopept with more than 100 known receptors conducted according to our protocol by the CEREP company (France) did not lead to the expected identification of the primary targets.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism Underlying the Action of Substituted Pro-Gly Dipeptide Noopept

et al. 2016

View full text Add to dashboard Cite

This study was performed in order to reveal the effect of Noopept (ethyl ester of N-phenylacetyl-Lprolylglycine, GVS-111) on the DNA-binding activity of transcriptional factors (TF) in HEK293 cells transiently transfected with luciferase reporter constructs containing sequences for CREB, NFAT, NF-κB, p53, STAT1, GAS, VDR, HSF1, and HIF-1. Noopept (10 μM) was shown to increase the DNA-binding activity of HIF-1 only, while lacking the ability to affect that of CREB, NFAT, NF-κB, p53, STAT1, GAS, VDR, and HSF1. Noopept provoked an additional increase in the DNA-binding activity of HIF-1 when applied in conditions of CoCl2-induced HIF- 1 stabilization. The degree of this HIF-positive effect of Noopept was shown to be concentration-dependent. Piracetam (1 mM) failed to affect significantly any of the TF under study. The results of molecular docking showed that Noopept (L-isomer), as well as its metabolite, L-isomer of N-phenyl-acetylprolyl, unlike its pharmacologically ineffective D-isomer, is able to bind to the active site of prolyl hydroxylase 2. Taking into account the important role of the genes activated by HIF-1 in the formation of an adaptive response to hypoxia, data on the ability of Noopept to provoke a selective increase in the DNA-binding activity of HIF-1 explain the wide spectrum of neurochemical and pharmacological effects of Noopept revealed before. The obtained data allow one to propose the HIF-positive effect as the primary mechanism of the activity of this Pro-Gly-containing dipeptide.

show abstract

Section: Introductionmentioning

confidence: 99%