Maxim Lovat
@bio.msu.ru
biology faculty
Lomonocov Moscow State Univercity
RESEARCH, TEACHING, or OTHER INTERESTS
Behavioral Neuroscience, Drug Discovery, Physiology
Scopus Publications
Scopus Publications
Olga A. Averina, Oleg A. Permyakov, Mariia A. Emelianova, Ekaterina A. Guseva, Olga O. Grigoryeva, Maxim L. Lovat, Anna E. Egorova, Andrei V. Grinchenko, Vadim V. Kumeiko, Maria V. Marey,et al.
MDPI AG
A small protein, Mitoregulin (Mtln), localizes in mitochondria and contributes to oxidative phosphorylation and fatty acid metabolism. Mtln knockout mice develop obesity on a high-fat diet, demonstrating elevated cardiolipin damage and suboptimal creatine kinase oligomerization in muscle tissue. Kidneys heavily depend on the oxidative phosphorylation in mitochondria. Here we report kidney-related phenotypes in aged Mtln knockout mice. Similar to Mtln knockout mice muscle mitochondria, those of the kidney demonstrate a decreased respiratory complex I activity and excessive cardiolipin damage. Aged male mice carrying Mtln knockout demonstrated an increased frequency of renal proximal tubules’ degeneration. At the same time, a decreased glomerular filtration rate has been more frequently detected in aged female mice devoid of Mtln. An amount of Mtln partner protein, Cyb5r3, is drastically decreased in the kidneys of Mtln knockout mice.
Olga A. Averina, Oleg A. Permyakov, Mariia A. Emelianova, Olga O. Grigoryeva, Maxim L. Lovat, Anna E. Egorova, Andrei V. Grinchenko, Vadim V. Kumeiko, Maria V. Marey, Vasily N. Manskikh,et al.
MDPI AG
Small peptides compose a large share of the mitochondrial proteome. Mitoregulin (Mtln) is a mitochondrial peptide known to contribute to the respiratory complex I functioning and other processes in mitochondria. In our previous studies, we demonstrated that Mtln knockout mice develop obesity and accumulate triglycerides and other oxidation substrates in serum, concomitant with an exhaustion of tricarboxylic acids cycle intermediates. Here we examined the functional role of Mtln in skeletal muscles, one of the major energy consuming tissues. We observed reduced muscle strength for Mtln knockout mice. Decrease of the mitochondrial cardiolipin and concomitant increase in monolysocardiolipin concentration upon Mtln inactivation is likely to be a consequence of imbalance between oxidative damage and remodeling of cardiolipin. It is accompanied by the mitochondrial creatine kinase octamer dissociation and suboptimal respiratory chain performance in Mtln knockout mice.
Olga A. Averina, Oleg A. Permyakov, Mariia A. Emelianova, Olga O. Grigoryeva, Mikhail V. Gulyaev, Olga S. Pavlova, Sofia S. Mariasina, Olga Yu Frolova, Marina V. Kurkina, Galina V. Baydakova,et al.
Elsevier BV
Anton V. Malyshev, Iuliia A. Sukhanova, Alexander S. Zlobin, Vasilina R. Gedzun, Vsevolod V. Pavshintsev, Ekaterina V. Vasileva, Arthur O. Zalevsky, Igor I. Doronin, Nikita A. Mitkin, Andrey V. Golovin,et al.
Frontiers Media SA
The aim of the study was to develop better anxiolytics and antidepressants. We focused on GABAAreceptors and the α2δ auxiliary subunit of V-gated Ca2+channels as putative targets because they are established as mediators of efficacious anxiolytics, antidepressants, and anticonvulsants. We further focused on short peptides as candidate ligands because of their high safety and tolerability profiles. We employed a structural bioinformatics approach to develop novel tetrapeptides with predicted affinity to GABAAreceptors and α2δ.In silicodocking studies of one of these peptides, LCGA-17, showed a high binding score for both GABAAreceptors and α2δ, combined with anxiolytic-like properties in aDanio reriobehavioral screen. LCGA-17 showed anxiolytic-like effects in the novel tank test, the light–dark box, and the social preference test, with efficacy comparable to fluvoxamine and diazepam. In binding assays using rat brain membranes, [3H]-LCGA-17 was competed more effectively by gabapentinoid ligands of α2δ than ligands of GABAAreceptors, suggesting that α2δ represents a likely target for LCGA-17. [3H]-LCGA-17 binding to brain lysates was unaffected by competition with ligands for GABAB, glutamate, dopamine, serotonin, and other receptors, suggesting specific interaction with α2δ. Dose-finding studies in mice using acute administration of LCGA-17 (i.p.) demonstrated anxiolytic-like effects in the open field test, elevated plus maze, and marble burying tests, as well as antidepressant-like properties in the forced swim test. The anxiolytic effects were effectively blocked by bicuculline. Therefore, LCGA-17 is a novel candidate anxiolytic and antidepressant that may act through α2δ, with possible synergism by GABAAreceptors.
Vlad S. Kuzmin, Viktoriia M. Potekhina, Yulia G. Odnoshivkina, Maria A. Chelombitko, Artem V. Fedorov, Olga A. Averina, Alexey S. Borodkov, Anna A. Shevtsova, Maxim L. Lovat, and Alexey M. Petrov
Elsevier BV
V. B. Vays, I. M. Vangeli, O. A. Averina, M. L. Lovat, and L. E. Bakeeva
Pleiades Publishing Ltd
Nikita A. Mitkin, Petr K. Anokhin, Maria V. Belopolskaya, Olga Y. Frolova, Ekaterina A. Kushnir, Maxim L. Lovat, and Vsevolod V. Pavshintsev
Elsevier BV
Arthur Zalevsky, Alexander Zlobin, Vasilina Gedzun, Roman Reshetnikov, Maxim Lovat, Anton Malyshev, Igor Doronin, Gennady Babkin, and Andrey Golovin
MDPI AG
Peptides are promising drug candidates due to high specificity and standout safety. Identification of bioactive peptides de novo using molecular docking is a widely used approach. However, current scoring functions are poorly optimized for peptide ligands. In this work, we present a novel algorithm PeptoGrid that rescores poses predicted by AutoDock Vina according to frequency information of ligand atoms with particular properties appearing at different positions in the target protein’s ligand binding site. We explored the relevance of PeptoGrid ranking with a virtual screening of peptide libraries using angiotensin-converting enzyme and GABAB receptor as targets. A reasonable agreement between the computational and experimental data suggests that PeptoGrid is suitable for discovering functional leads.
V. V. Pavshintsev, L. S. Podshivalova, O. Y. Frolova, M. V. Belopolskaya, O. A. Averina, E. A. Kushnir, N. V. Marmiy, and M. L. Lovat
Pleiades Publishing Ltd
Vsevolod V. Pavshintsev, Nikita A. Mitkin, Olga Y. Frolova, Ekaterina A. Kushnir, Olga A. Averina, and Maxim L. Lovat
Elsevier BV
M. L. Lovat, M. Sh. Avrushchenko, O. A. Averina, V. V. Pavshintsev, I. V. Ostrova, Y. V. Zarzhetsky, V. V. Moroz, and M. V. Egorov
FSBI SRIGR RAMS
The aim was to assess the efficacy of mitochondriatargeted antioxidant SkQ1 in prevention of structural and functional abnormalities of brain postresuscitation after cardiac arrest. Materials and methods. Adult male Wistar rats (n=19) underwent cardiac arrest for 7 minutes followed by resuscitation. Nine rats were administered with 500 nmol/kg SkQ1 per os with water for 2 weeks (1 week before and 1 week after resuscitation). A control group consisted of shamoperated animals (n=10). At days 4—6 post operation locomotor activity and anxiety («elevated plus maze» test) and sensorimotor function of limbs («beam walking» test) were examined. Total numbers of neurons per 1 mm of their layer length in vulnerable neuronal populations (cerebellar Purkinje cells and piramidal neurons of hippocampus fields CA1 and CA4) were estimated by histological analysis of the specimens stained with cresyl violet on day 7 postresuscitation. To identify possible mechanisms of SkQ1 action, the immunohistochemical study of a glialderived neurotrophic factor (GDNF) expression in piramidal neurons of hippocampus was performed by indirect peroxidaseantiperoxidase method and antiGDNF primary polyclonal antibodies. Results . Ischemiareperfusion resulted in neuronal loss in all studied brain areas followed by reduction in locomotor activity and development of sensorimotor deficit. SkQ1 prevented development of postresuscitative locomotor and sensorimotor irregularities, significantly reduced Purkinje cells loss, prevented death of piramidal neurons in hippocampal field CA4, but not in CA1. Data demonstrated, that iIn Purkinje cells from resuscitated rats treated with SkQ1 there was a significant increase in number of GDNFpositive neurons, which were more resistant to ischemia (transition of GDNFnegative cells toward the category of cells actively expressing this factor) that promoted their survival postresuscitation. Conclusion. Data confirm the positive effects of SkQ1 on structural and functional status of the brain postre suscitation and suggest possible use of SkQ1 for the prevention or correction of posthypoxic encephalopathies.
Alexander A. Andreev-Andrievskiy, Nataliya G. Kolosova, Natalia A. Stefanova, Maxim V. Lovat, Maxim V. Egorov, Vasily N. Manskikh, Roman A. Zinovkin, Ivan I. Galkin, Anastasia S. Prikhodko, Maxim V. Skulachev,et al.
Hindawi Limited
Rheumatoid arthritis is one of the most common autoimmune diseases. Many antioxidants have been tested in arthritis, but their efficacy was, at best, marginal. In this study, a novel mitochondria-targeted antioxidant, plastoquinonyl-decyl-triphenylphosphonium bromide (SkQ1), was testedin vivoto prevent and cure experimental autoimmune arthritis. In conventional Wistar rats, SkQ1 completely prevented the development of clinical signs of arthritis if administered with food before induction. Further, SkQ1 significantly reduced the fraction of animals that developed clinical signs of arthritis and severity of pathological lesions if administration began immediately after induction of arthritis or at the onset of first symptoms (day 14 after induction). In specific pathogen-free Wistar rats, SkQ1 administered via gavage after induction of arthritis did not reduce the fraction of animals with arthritis but decreased the severity of lesions upon pathology examination in a dose-dependent manner. Efficacious doses of SkQ1 were in the range of 0.25–1.25 nmol/kg/day (0.13–0.7 μg/kg/day), which is much lower than doses commonly used for conventional antioxidants. SkQ1 promoted apoptosis of neutrophilsin vitro, which may be one of the mechanisms underlying its pharmacological activity. Considering its low toxicity and the wide therapeutic window, SkQ1 may be a valuable additional therapy for rheumatoid arthritis.
Anastasia Graf, Lidia Trofimova, Alexandra Loshinskaja, Garik Mkrtchyan, Anastasiia Strokina, Maxim Lovat, Adam Tylicky, Slawomir Strumilo, Lucien Bettendorff, and Victoria I. Bunik
Elsevier BV
L. Trofimova, M. Lovat, A. Groznaya, E. Efimova, T. Dunaeva, M. Maslova, A. Graf, and V. Bunik
Hindawi Limited
Decreased activity of the mitochondrial 2-oxoglutarate dehydrogenase complex (OGDHC) in brain accompanies neurodegenerative diseases. To reveal molecular mechanisms of this association, we treated rats with a specific inhibitor of OGDHC, succinyl phosphonate, or exposed them to hypoxic stress. In males treated with succinyl phosphonate and in pregnancy-sensitized females experiencing acute hypobaric hypoxia, we revealed upregulation of brain OGDHC (within 24 hours), with the activity increase presumably representing the compensatory response of brain to the OGDHC inhibition. This up-regulation of brain OGDHC was accompanied by an increase in exploratory activity and a decrease in anxiety of the experimental animals. Remarkably, the hypoxia-induced elevation of brain OGDHC and most of the associated behavioral changes were abrogated by succinyl phosphonate. The antagonistic action of hypoxia and succinyl phosphonate demonstrates potential therapeutic significance of the OGDHC regulation by the phosphonate analogs of 2-oxoglutarate.
V. A. Isaev, R. A. Danilova, E. A. Kushnir, M. L. Lovat', and I. P. Ashmarin
Springer Science and Business Media LLC
R. A. Danilova, V. N. Prozorovskii, T. A. Moskvitina, M. F. Obukhova, M. L. Lovat', I. M. Fedorova, and I. P. Ashmarin
Springer Science and Business Media LLC