The cognitive-stimulating, neuroprotective effects of promising fluorinated tetrahydrocarbazole derivatives (CA-7043x and CA-7050x) on the hippocampus-dependent memory of outbred mice (CD1) and transgenic Tg6799 mice, as well as their effect on anxiety, locomotor activity, and orienting-exploratory behavior of animals, were studied. It was found that both compounds have a pronounced cognitive-stimulating effect on CD1 mice, but do not show neuroprotective effects on memory support in Tg6799 mice. It is noted that, in the open-field test, the CA-7050x compound has a positive effect on the orientating behavior, and the CA-7043x compound has a positive effect on the exploratory response in the nontransgenic control.

New peptides analogues of Semax can potentiate AMPA receptors induced currents at lower concentrations (10–11–10–8 M) than those of Semax. This ability suggests that they may have cognitive-stimulating properties.

Intracellular and extracellular accumulation of fibrillary proteins, beta-amyloid and hyperphosphorylated Tau, in patients with Alzheimer’s disease (AD) leads to chronic and progressive neurodegenerative process. Overaccumulation of aggregates results in synaptic dysfunction and inevitable neuronal loss. Although the exact molecular pathways of the AD still require better understanding, it is clear this neuropathology is a multifactorial disorder where the advanced age is the main risk factor. Lately, several dozens of drug candidates have succeeded to phase II clinical trials; however, none has passed phase III. In this review we summarize existing data on anti-AD therapeutic agents currently undergoing clinical trials and included in the public websites www.clinicaltrials.gov and Alzforum.org as well as the Thomson Reuters «Integrity» database. We revealed three major trends in AD drug discovery. First, developing of “disease-modifying agents” could potentially slow the progression of structural and functional abnormalities in the central nervous system providing sustainable improvements of cognitive functions, which persist even after drug withdrawal. Secondly, the focused design of multitargeted drugs acting on multiple key molecular pathways. Finally, the repositioning of drugs that are already available on the market for the novel (anti-AD) application provides a promising strategy for finishing clinical trials and re-marketing.

The obtained results show that endogenous peptides play an important role in the regulation of the glutamatergic mediator system of the brain. They act in extremely low concentrations, starting at 1 × 10–14 M, their effects are concentration-dependent and reversible, thus indicating the exclusive specificity of the corresponding receptors. The range of their influence on responses of postsynaptic glutamate receptors is rather narrow and, as a rule, does not exceed 60-70% of control. We have demonstrated for the first time that CLIP blocks NMDA receptors and potentiates AMPA receptors in a wide range of concentrations (6 orders of magnitude); this is very important for manifestation of memory-stimulating effect. Somatostatin blocking NMDA receptors and potentiating AMPA receptors, also plays an important role in the mechanisms of memory formation. Obviously, there is a great similarity in the action of both peptides on AMPA and NMDA receptors. Thus our results provide the first information about regulation of including cognitive processes and memory mechanisms by endogenous compounds. This mechanism particularly involves regulation of AMPA and NMDA receptors in the brain.

The study is devoted to the development of an artificial material based on the ultrahigh-molecular weight polyethylene (UHMWPE) with a porous or cellular 3D structure as a cellular matrix – a framework for growing cell cultures. The development of such matrix provides support for neuronal cell culture under conditions that mimick those that exist in the living body. Typically, in vitro cellular studies are conducted in a 2D format, which limits intercellular interactions, morphology, differentiation, survival, signaling responses, gene expression and proliferation that are found in vivo. Here, we propose to use UHMWPE as a material of the cellular matrix, the ultra-high molecular weight polyethylene. UHMWP is a bioinert substance, wich allows forming a system of open connected pores needed to provide cellular life conditions with supply of nutrients and oxygen as well as the removal of waste products, the possibility of intercellular communication, etc. As a result, the use of UHMWPE as a cellular matrix will allow to study the processes occurring in cells in the 3D environment.

The presence of calcium-activated chloride current was shown using on freshly isolated rat Purkinje cerebellum neiurones and the pacth-clamp method in the whole-cell configuration. Chloride currents appeared in sodium-free external solution and reversibly disappeared in chloride-free or calcium-free external solution. Replacing of K+ ions (120 mM) to Cs+ ions in micropipette (120 mM) show the chloride currents even with 140 mM Na+ in external solution. This current was blocked to 80–100% by nifluminic acid (25–100 ΜM). It was found out that well known blockers of potassium channels tetraethylammonium (TEA) and 4-aminopyridine (4-AP) also effectively blocked chloride channels. The IC50 values for TEA and 4-AP were 130 ΜM, and 110 ΜM respectively. The action of TEA was reversible, while 4-AP at concentration 100 ΜM and above irreversibly blocked chloride channels.