Ivan B Filippenkov, Julia A Remizova, Vasily V Stavchansky, Alina E Denisova, Leonid V Gubsky, Nikolay F Myasoedov, Svetlana A Limborska, Lyudmila V Dergunova
Ischemic stroke is an acute local decrease in cerebral blood flow due to a thrombus or embolus. Of particular importance is the study of the genetic systems that determine the mechanisms underlying the formation and maintenance of a therapeutic window (a time interval of up to 6 h after a stroke) when effective treatment can be provided. Here, we used a transient middle cerebral artery occlusion (tMCAO) model in rats to study two synthetic derivatives of adrenocorticotropic hormone (ACTH). The first was ACTH(4-7)PGP, which is known as Semax...
June 30, 2023: Genes
Tatiana V Vyunova, Ludmila A Andreeva, Konstantin V Shevchenko, Nataliya Yu Glazova, Elena A Sebentsova, Natalia G Levitskaya, Nikolay F Myasoedov
The central effectors of the stress system are greatly interconnected and include, among others, a large group of peptides derived from proopiomelanocortin. In addition to natural corticotropins, a number of artificial molecules that contain some ACTH fragments in their structure are also referred to members of this family. Some of them possess a wide range of biological activity. The molecular mechanism underlying the biological activity of such peptides is partly based on allosteric modulation of various receptors...
June 2023: Chemical Biology & Drug Design
Vasily V Stavchansky, Ivan B Filippenkov, Julia A Remizova, Alina E Denisova, Ivan V Mozgovoy, Leonid V Gubsky, Nikolay F Myasoedov, Lyudmila A Andreeva, Svetlana A Limborska, Lyudmila V Dergunova
Glyprolines are Gly-Pro (GP)- or Pro-Gly (PG)-containing biogenic peptides. These peptides can act as neutrophil chemoattractants, or atheroprotective, anticoagulant, and neuroprotective agents. The Pro-Gly-Pro (PGP) tripeptide is an active factor of resistance to the biodegradation of peptide drugs. The synthetic Semax peptide, which includes Met-Glu-His-Phe (MEHF) fragments of adrenocorticotropic hormone and the C-terminal tripeptide PGP, serves as a neuroprotective drug for the treatment of ischemic stroke...
December 16, 2022: Genes
A K Dragon, N B Korchazhkina, V M Sheludchenko, Yu Yusef, J V Kosova, M A Makarova, M A Elfimov
Optical neuropathies (ON) are the outcome of many diseases of various origins. The main ones are classified as inflammatory, vascular and traumatic ON. ON lead to subatrophy of the optic nerve, but even after the completion of treatment, it is possible to improve visual functions by using physiotherapeutic means of ophthalmic rehabilitation. OBJECTIVE: To evaluate the effectiveness of complex physiotherapeutic neuro-ophthalmostimulation in case of ON of vascular origin. MATERIAL AND METHODS: The study included 60 patients (120 eyes) with a verified diagnosis of optic neuropathy of vascular origin, who were divided into 2 groups comparable in age, gender and anatomical and functional characteristics: the main group of 30 patients (60 eyes) and the control group - 30 patients (60 eyes), including 24 men and 36 women, mean age was 66...
2022: Voprosy Kurortologii, Fizioterapii, i Lechebnoĭ Fizicheskoĭ Kultury
Michele F M Sciacca, Irina Naletova, Maria Laura Giuffrida, Francesco Attanasio
Alzheimer's disease, the most common form of dementia, is characterized by the aggregation of amyloid beta protein (Aβ). The aggregation and toxicity of Aβ are strongly modulated by metal ions and phospholipidic membranes. In particular, Cu2+ ions play a pivotal role in modulating Aβ aggregation. Although in the last decades several natural or synthetic compounds were evaluated as candidate drugs, to date, no treatments are available for the pathology. Multifunctional compounds able to both inhibit fibrillogenesis, and in particular the formation of oligomeric species, and prevent the formation of the Aβ:Cu2+ complex are of particular interest...
February 16, 2022: ACS Chemical Neuroscience
A A Kolacheva, M V Ugrumov
Degeneration of nigrostriatal dopaminergic neurons in Parkinson's disease begins from the axonal terminals in the striatum and, then, in retrograde fashion, progresses to the cell bodies in the substantia nigra. Investigation of the dynamics of axonal terminal degeneration may help in the identification of new targets for neuroprotective treatment and be used as a tool for testing potential drugs. We have shown that the degeneration rate of dopaminergic axonal terminals changes over time, and that the striatal dopamine concentration is the most sensitive parameter to the action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
July 2021: Acta Naturae
Ivan B Filippenkov, Vasily V Stavchansky, Natalya Yu Glazova, Elena A Sebentsova, Julia A Remizova, Liya V Valieva, Natalia G Levitskaya, Nikolai F Myasoedov, Svetlana A Limborska, Lyudmila V Dergunova
Natural melanocortins (MCs) have been used in the successful development of drugs with neuroprotective properties. Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP under normal and acute restraint stress (ARS) conditions. Administration of Semax or ACTH(6-9)PGP (100 μg/kg) to rats 30 min before ARS attenuated ARS-induced behavioral alterations. Using high-throughput RNA sequencing (RNA-Seq), we identified 1359 differentially expressed genes (DEGs) in the hippocampus of vehicle-treated rats subjected to ARS, using a cutoff of >1...
September 17, 2021: International Journal of Molecular Sciences
Ihnat O Havrylov Phd Student, Serg Y Shtrygol Md Phd Dsc Professor
The article presents a study of the effect of a modified fragment of neuropeptide Y (H-L-Ile-L-Asn-L-Leu-L-Nle-L-Ser- L-Arg-L-Asn-L-Arg-L-Tyr-NH2) named nonapeptide NP9 on the memory phases and extrapolation escape of animals. The study was performed in the passive avoidance test with intact animals, scopolamine-treated animals, and the extrapolation escape task. NP9 was investigated in the dose range of 0.04-0.4 mg/kg with a single intranasal administration. The comparison drug used peptide nootropic medicine Semax® (Met-Glu-His-Phe-Pro-Gly-Pro) at a dose of 0...
2021: Ceská a Slovenská Farmacie
Olga Yu Sudarkina, Ivan B Filippenkov, Vasily V Stavchansky, Alina E Denisova, Vadim V Yuzhakov, Larisa E Sevan'kaeva, Liya V Valieva, Julia A Remizova, Veronika G Dmitrieva, Leonid V Gubsky, Nikolai F Myasoedov, Svetlana A Limborska, Lyudmila V Dergunova
The Semax (Met-Glu-His-Phe-Pro-Gly-Pro) peptide is a synthetic melanocortin derivative that is used in the treatment of ischemic stroke. Previously, studies of the molecular mechanisms underlying the actions of Semax using models of cerebral ischemia in rats showed that the peptide enhanced the transcription of neurotrophins and their receptors and modulated the expression of genes involved in the immune response. A genome-wide RNA-Seq analysis revealed that, in the rat transient middle cerebral artery occlusion (tMCAO) model, Semax suppressed the expression of inflammatory genes and activated the expression of neurotransmitter genes...
June 8, 2021: International Journal of Molecular Sciences
L V Dergunova, V G Dmitrieva, I B Filippenkov, V V Stavchansky, A E Denisova, V V Yuzhakov, L E Sevan'kaeva, L V Valieva, O Y Sudarkina, L V Gubsky, N F Myasoedov, S A Limborska
Due to its nootropic, neuroprotective, and immunomodulatory effects, the peptide Semax is utilized in the treatment of ischemic stroke. Our earlier RNA-Seq analysis of the transcriptome in an ischemic model of transient occlusion of the middle cerebral artery showed an increase in the mRNA levels of many proinflammatory genes, and the suppression of their induction by Semax. However, for many relevant genes, including Il1a, Il1b, Il6 and Tnfa, the levels of their expression were too low for detailed quantitative evaluation...
May 2021: Molekuliarnaia Biologiia
Fatima M Shakova, Yuliya I Kirova, Denis N Silachev, Galina A Romanova, Sergey G Morozov
The pharmacological induction and activation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a key regulator of ischemic brain tolerance, is a promising direction in neuroprotective therapy. Pharmacological agents with known abilities to modulate cerebral PGC-1α are scarce. This study focused on the potential PGC-1α-modulating activity of Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) and Semax (ACTH(4-7) analog) in a rat model of photochemical-induced thrombosis (PT) in the prefrontal cortex...
March 4, 2021: Brain Sciences
M V Svishcheva, Ye S Mishina, O A Medvedeva, I I Bobyntsev, A Y Mukhina, P V Kalutskii, L A Andreeva, N F Myasoedov
We studied the effect of intraperitoneal administration ACTH(4-7) -PGP in doses of 5, 50, 150, and 450 μg/kg to Wistar male rats 12-15 min before modeling restraint stress on the morphofunctional state of the colon. In rats exposed to restraint stress, signs of atrophy and inflammatory reaction in the colon wall, changes in functional activity and number of mast cells, and increased serum level of corticosterone were observed. Administration of the peptide led to a decrease in corticosterone concentration, alleviated stress-induced pathomorphological changes, and promoted adaptation of the intestinal wall to stress...
January 2021: Bulletin of Experimental Biology and Medicine
Nataliya Yu Glazova, Daria M Manchenko, Maria A Volodina, Svetlana A Merchieva, Ludmila A Andreeva, Vladimir S Kudrin, Nikolai F Myasoedov, Natalia G Levitskaya
Selective serotonin reuptake inhibitors (SSRI) are commonly used to treat depression during pregnancy. SSRIs cross the placenta and may influence the maturation of the foetal brain. Clinical and preclinical findings suggest long-term consequences of SSRI perinatal exposure for the offspring. The mechanisms of SSRI effects on developing brain remain largely unknown and there are no directional approaches for prevention of the consequences of maternal SSRI treatment during pregnancy. The heptapeptide Semax (MEHFPGP) is a synthetic analogue of ACTH(4-10) which exerts marked nootropic and neuroprotective activities...
April 2021: Neuropeptides
L A Severyanova, A A Kryukov, D V Plotnikov, M E Dolgintsev
The effects of peptide ACTH4-7-PGP (Semax) were studied in 12 min after its intraperitoneal (in doses of 5, 15, 50, 150, and 450 μg/kg) or intracerebroventricular (in doses of 16, 40, and 400 pg) administration to rats with different types of pain and pain-induced behavior. It was found that the peptide increased pain sensitivity and induced avoidance behavior during thermal stimulation ("hot plate" test), but had an analgesic effect (more pronounced after central administration) and weakened emotional-affective behavior in electrocutaneous stimulation of the paws (foot-shock model) and tail in rats...
December 2020: Bulletin of Experimental Biology and Medicine
M V Svishcheva, A Yu Mukhina, O A Medvedeva, A V Shevchenko, I I Bobyntsev, P V Kalutskii, L A Andreeva, N F Myasoedov
We studied the effect of Semax on the state of intestinal microbiota in rats subjected to restraint stress. Semax was injected to Wistar male rats intraperitoneally in doses of 5, 50, 150, 450 μg/kg 12-15 min before modelling chronic restraint stress. It was found that stress exposure reduced the number of obligate bacteria in the colon microbiota, but increased the content of opportunistic microorganisms. Semax in doses of 50 and 150 μg/kg prevented the stress-induced changes in the composition of colon microbiota...
August 1, 2020: Bulletin of Experimental Biology and Medicine
Ivan B Filippenkov, Vasily V Stavchansky, Alina E Denisova, Vadim V Yuzhakov, Larisa E Sevan'kaeva, Olga Y Sudarkina, Veronika G Dmitrieva, Leonid V Gubsky, Nikolai F Myasoedov, Svetlana A Limborska, Lyudmila V Dergunova
Cerebral ischaemia is the most common cause of impaired brain function. Biologically active peptides represent potential drugs for reducing the damage that occurs after ischaemia. The synthetic melanocortin derivative, ACTH(4-7) PGP (Semax), has been used successfully in the treatment of patients with severe impairment of cerebral blood circulation. However, its molecular mechanisms of action within the brain are not yet fully understood. Previously, we used the transient middle cerebral artery occlusion (tMCAO) model to study the damaging effects of ischaemia-reperfusion on the brain transcriptome in rats...
June 22, 2020: Genes
Ya R Panikratova, I S Lebedeva, O Yu Sokolov, A D Rumshiskaya, D A Kupriyanov, N V Kost, N F Myasoedov
The present study was aimed at the assessment of effects of anxiolytic Selank and nootropic Semax on the whole-brain resting-state functional connectivity (FC) of each of the predefined regions of interest (ROIs) in 52 healthy participants. The ROIs included amygdala (one of the key regions for the regulation of anxiety) and dorsolateral prefrontal cortex (DLPFC; the key region for executive functions, including working memory) in the right and left hemisphere. Resting-state fMRI was carried out three times, namely before, after 5 and 20 min of the injection of either Semax, or Selank, or placebo...
January 2020: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
A A Elagina, Yu D Lyashev, A Yu Lyashev, T V Pronyaeva, A R Chahine
We studied the effect of peptide drugs deltalicin and Semax on lipid metabolism disturbances in diabetes mellitus. Diabetes mellitus was modeled by single injection of streptozotocin (45 mg/kg) and rats with blood glucose ≥12 mmol/liter were selected for the further experiments. Deltalicin in a dose 100 μg/kg and Semax in a dose 200 μg/kg as well as sulodexide corrected lipid metabolism disorders: the content of total cholesterol, triglycerides, LDL, index of atherogenicity decreased and HDL concentration increased...
April 4, 2020: Bulletin of Experimental Biology and Medicine
E V Novosadova, E L Arsenyeva, S A Antonov, Y N Vanyushina, T V Malova, A A Komissarov, S N Illarioshkin, L G Khaspekov, L A Andreeva, N F Myasoedov, V Z Tarantul, I A Grivennikov
Development of therapeutic preparations involves several steps, starting with the synthesis of chemical compounds and testing them in different models for selecting the most effective and safest ones to clinical trials and introduction into medical practice. Cultured animal cells (both primary and transformed) are commonly used as models for compound screening. However, cell models display a number of disadvantages, including insufficient standardization (primary cells) and disruption of cell genotypes (transformed cells)...
November 2019: Biochemistry. Biokhimii︠a︡
T V Vyunova, L A Andreeva, K V Shevchenko, N F Myasoedov
An integrated methodological approach to study the molecular aspects of short regulatory neuropeptides biological mechanism is proposed. The complex research is based on radioligand-receptor method of analysis and covers such points of peptides molecular activity as: specific binding of peptides to brain cells plasmatic membranes, formation of tissue specific synacton, influence of peptides (as allosteric modulators) on functionality of different neuroreceptors as well as delayed in time effects of peptides on receptor-binding activity of well-known neuroreceptor systems...
July 20, 2019: Journal of Labelled Compounds & Radiopharmaceuticals
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