Neuroprotective Effect of the Neuropeptide Cycloprolylglycine Depends on AMPA- and TrkB-Receptor Activation.

Previously, we have shown that the endogenous neuropeptide cycloprolylglycine (CPG) is the positive modulator of AMPA receptors and revealed the dependence of its anxiolytic and antihypoxic action on BDNF/Trk signaling. In the present work, we for the first time conducted in vitro experiments using the AMPA receptor blockers DNQX and GYKI 52466 and the Trk receptor blocker K252a. It is shown that the neuroprotective effect of CPG depends on the activation of both AMPA and Trk receptors.

Low molecular weight NGF mimetic GK-2 normalizes the parameters of glucose and lipid metabolism and exhibits a hepatoprotective effect on a prediabetes model in obese Wistar rats.

Signs of metabolic syndrome and prediabetes preceding type 2 diabetes are modelled in an experiment using a high-fat diet (HFD). The aim of this work was to study the effect of a low molecular weight systemically active nerve growth factor mimetic, compound GK-2 (hexamethylenediamide bis[N-monosuccinyl-L-glutamyl-L-lysine]), on indicators of abdominal obesity, basal blood glucose level, glucose tolerance, cholesterol and triglyceride blood levels, as well as the morphological structure of the liver in male Wistar rats fed a HFD. Rats were divided into three groups: one of them received standard food (control) and two others were fed a HFD containing 45% fat, 35% carbohydrates and 20% protein, with a total caloric value of 516 kcal/100 g, over 12 weeks.

The Anxiolytic Effect of the Neuropeptide Cycloprolylglycine Is Mediated by AMPA and TrkB Receptors.

Previously we have shown that the neuropeptide cycloprolylglycine is an endogenous positive modulator of AMPA receptors and assumed that the pharmacological effects of CPG are associated with the brain neurotrophic factor. In this paper, we have first demonstrated that DNQX, an inhibitor of AMPA receptors, and K252A, an ihibitor of Trk receptors, prevented the anxiolytic effect of CPG, which confirms the formulated hypothesis.

Neuropeptide cycloprolylglycine is an endogenous positive modulator of AMPA receptors.

We have previously shown that neuropeptide cycloprolylglycine (CPG) increases the content of brain-derived neurotrophic factor (BDNF) in the culture of neuronal cells under normal conditions and in pathology. This is the first study to show that CPG at a physiological concentration of 10 M significantly enhances the transmembrane AMPA currents in rat cerebellar Purkinje cells. Thus, CPG is a positive endogenous modulator of AMPA receptors.

Neuropeptide cycloprolylglycine increases the levels of brain-derived neurotrophic factor in neuronal cells.

It was shown for the first time that the endogenous cyclic dipeptide cycloprolylglycine (CPG) at concentrations of 10(-7) and 10(-3) M and piracetam at a concentration of 10(-3) M increased the content of brainderived neurotrophic factor (BDNF) in the culture of neuronal cells in normal state and under conditions of glutamate and 6-oxydopamine neurotoxicity. This may indicate the possible involvement of BDNF in the mechanism of action of neuropeptide CPG and piracetam.