Biochemistry (Moscow)最新文献

{"title":"Evolution, Possibilities, and Prospects for Application of the Methods of Assessment of Pyridine Nucleotides Pool for Studying Mechanisms of Brain Plasticity in Normal and Pathological Conditions","authors":"Anna V. Zubova,&nbsp;Alexander A. Groshkov,&nbsp;Arsenii K. Berdnikov,&nbsp;Svetlana V. Novikova,&nbsp;Natalia A. Rozanova,&nbsp;Lyudmila V. Nikolaeva,&nbsp;Vladimir V. Salmin,&nbsp;Nataliya A. Kolotyeva,&nbsp;Leonid G. Khaspekov,&nbsp;Alla B. Salmina,&nbsp;Stanislav O. Yurchenko,&nbsp;Sergey N. Illarioshkin","doi":"10.1134/S0006297924604477","DOIUrl":"10.1134/S0006297924604477","url":null,"abstract":"<p>Nicotinamide adenine dinucleotide and its derivatives – NAD⁺, NADP⁺, NADH, NADPH – play an important role in cell metabolism, act as substrates or cofactors for a large number of enzymes involved in the DNA regulation of replication and repair, maintenance of calcium homeostasis in cells, biosynthetic processes, and energy production mechanisms. Changes in the ratio of oxidized and reduced forms of pyridine nucleotides accompanies development of oxidative and reductive stress that significantly contribute to the cell damage and induction of adaptive responses. Currently, a huge number of protocols aimed at quantitative or qualitative assessment of the pyridine nucleotide pool are in use, but all of them have their limitations associated with sample preparation processes, difficulties in the metabolite spectrum assessment, and complexity of data interpretation. Measuring pyridine nucleotide levels is relevant in the studies of pathophysiological regulatory mechanisms of the cell functional activity and intercellular communication. This is of particular relevance when studying the mechanisms of plasticity of the central nervous system in health and disease, since significant changes in the pools of pyridine nucleotides in cells are evident in neurodevelopmental disorders, neurodegeneration, and aging. Simple and reliable non-invasive methods for measuring levels of NAD⁺ and NADH are necessary to assess the brain cells metabolism with diagnostic and research purposes. The goal of this review is to conduct comparative analysis of the main methods for measuring the levels of oxidized and reduced pyridine nucleotides in cells and to identify key principles of their application for correct interpretation of the obtained data, including those used for studying central nervous system.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"231 - 246"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitors of Transketolase from Mycobacterium tuberculosis Targeted towards both the Diphosphate Binding Site and an Adjacent Hydrophobic Subsite","authors":"Dmitry K. Nilov,&nbsp;Irina V. Gushchina,&nbsp;Tatyana A. Shcherbakova,&nbsp;Simon M. Baldin,&nbsp;Vytas K. Švedas","doi":"10.1134/S000629792460354X","DOIUrl":"10.1134/S000629792460354X","url":null,"abstract":"<p>Transketolase from <i>Mycobacterium tuberculosis</i> (mbTK) is involved in the pentose phosphate pathway essential for bacterial survival and thus constitutes an attractive target for the antituberculosis therapy. We found a new class of active site-targeted furan sulfonate inhibitors of mbTK that are capable of binding to both the thiamine diphosphate cofactor subsite and adjacent hydrophobic subsite Ile211-Leu402-Phe464, thereby suppressing enzyme activity. The most potent compound identified by computer screening, STK106769, was found to inhibit mbTK with IC₅₀ of 7 µM and suppress the growth of <i>M. tuberculosis</i> H37Rv strain. The hydrophobic subsite Ile211-Leu402-Phe464 of mbTK is substituted by significantly more polar residues in homologous human TK, which is an important factor determining the selectivity of binding of TK inhibitors.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"259 - 264"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Neural Reprogramming in situ: Existing Approaches and Their Optimization","authors":"Nikita V. Dokukin,&nbsp;Daria A. Chudakova,&nbsp;Matvey O. Shkap,&nbsp;Anna M. Kovalchuk,&nbsp;Pavel D. Kibirsky,&nbsp;Vladimir P. Baklaushev","doi":"10.1134/S000629792460426X","DOIUrl":"10.1134/S000629792460426X","url":null,"abstract":"<p>Direct <i>in situ</i> neuronal reprogramming (transdifferentiation) of glial cells (astrocytes and microglia) has attracted a significant interest as a potential approach for the treatment of a wide range of neurodegenerative diseases and damages of the central nervous system (CNS). The nervous system of higher mammals has a very limited capacity for repair. Disruption of CNS functioning due to traumatic injuries or neurodegenerative processes can significantly affect the quality of patients’ life, lead to motor and cognitive impairments, and result in disability and, in some cases, death. Restoration of lost neurons <i>in</i> <i>situ</i> via direct reprogramming of glial cells without the intermediate stage of pluripotency seems to be the most attractive approach from the viewpoint of translational biomedicine. The ability of astroglia to actively proliferate in response to the damage of neural tissue supports the idea that these neuron-like cells, which are already present at the lesion site, are good candidates for transdifferentiation into neurons, considering that the possibility of direct neuronal reprogramming of astrocytes both <i>in</i> <i>vitro</i> and <i>in</i> <i>vivo</i> have demonstrated in many independent studies. Overexpression of proneuronal transcription factors, e.g., neurogenic differentiation factors 1-4 (NeuroD1-4), Neurogenin 2 (NeuroG2), Ascl1 (Achaete-Scute homolog 1), and Dlx2 (distal-less homeobox 2), including pioneer transcription factors that recognize target sequences in the compacted chromatin and activate transcription of silent genes, has already been proven as a potential therapeutic strategy. Other strategies, such as microRNA-mediated suppression of activity of PTB and REST transcription factors and application of small molecules or various biomaterials, are also utilized in neuronal reprogramming. However, the efficiency of direct <i>in</i> <i>situ</i> reprogramming is limited by a number of factors, including cell specificity of transgene delivery systems and promoters, brain regions in which transdifferentiation occurs, factors affecting cell metabolism, microenvironment, etc. Reprogramming <i>in</i> <i>situ</i>, which takes place in the presence of a large number of different cell types, requires monitoring and precise phenotypic characterization of subpopulations of cells undergoing transdifferentiation in order to confirm the reprogramming of the astroglia into neurons and subsequent integration of these neurons into the CNS. Here, we discussed the most efficient strategies of neuronal reprogramming and technologies used to visualize the transdifferentiation process, with special focus on the obstacles to efficient neuronal conversion, as well as approaches to overcome them.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"214 - 230"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymeric Drug Delivery Systems in Biomedicine","authors":"Ivan A. Gulyaev,&nbsp;Maria B. Sokol,&nbsp;Mariia R. Mollaeva,&nbsp;Maksim A. Klimenko,&nbsp;Nikita G. Yabbarov,&nbsp;Margarita V. Chirkina,&nbsp;Elena D. Nikolskaya","doi":"10.1134/S0006297924603976","DOIUrl":"10.1134/S0006297924603976","url":null,"abstract":"<p>Our review examines the key aspects of using polymeric carriers in biomedicine. The section “Polymers for Biomedicine” provides an overview of different types of polymers, their structural features and properties that determine their use as drug delivery vehicles. The section “Polymeric Carriers” characterizes the role of polymeric delivery systems in modern medicine. The main forms of polymeric carriers are described, as well as their key advantages for drug delivery. The section “Preclinical and Clinical Trials of Polymeric Drug Carriers” reviews the examples of clinical and preclinical studies of polymeric forms used for antitumor therapy, therapy for bacterial and infectious diseases. The final section “Targeted Drug Delivery Systems” is devoted to the discussion of approaches, as well as ligands that provide targeted drug delivery using polymeric carriers. We have paid special attention to modern approaches for increasing the efficacy of antibacterial therapy using vector molecules.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S233 - S262"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Aging Clocks” Based on Cell-Free DNA","authors":"Aleksandr V. Sergeev,&nbsp;Olga V. Kisil,&nbsp;Andrey A. Eremin,&nbsp;Aleksandr S. Petrov,&nbsp;Maria E. Zvereva","doi":"10.1134/S0006297924604076","DOIUrl":"10.1134/S0006297924604076","url":null,"abstract":"<p>Aging is associated with systemic changes in the physiological and molecular parameters of the body. These changes are referred to as biomarkers of aging. Statistical models that link changes in individual biomarkers to biological age are called aging clocks. These tools facilitate a comprehensive evaluation of bodily health and permit the quantitative determination of the rate of aging. A particularly promising area for the development of aging clocks is the analysis of cell-free DNA (cfDNA), which is present in the blood and contains numerous potential biomarkers. This review explores in detail the fragmentomics, topology, and epigenetic landscape of cfDNA as possible biomarkers of aging. The review further underscores the potential of leveraging single-molecule sequencing of cfDNA in conjunction with long-read technologies to simultaneously profile multiple biomarkers, a strategy that could lead to the development of more precise aging clocks.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S342 - S355"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fo∙F1 ATP-synthase/ATPase of Paracoccus denitrificans: Mystery of Unidirectional Catalysis","authors":"Tatiana V. Zharova,&nbsp;Vera G. Grivennikova","doi":"10.1134/S000629792460399X","DOIUrl":"10.1134/S000629792460399X","url":null,"abstract":"<p>F_o∙F₁ ATP synthases/ATPases (F_o∙F₁) catalyze ATP synthesis by consuming energy of electrochemical potential of hydrogen ions (<i>pmf)</i>, or ATP hydrolysis resulting in the <i>pmf</i> formation. It is generally accepted to consider F_o∙F₁ as a reversible chemomechanical-electrical molecular machine, however: (i) the mechanism of energy-dependent ATP synthesis is based only on the data on hydrolytic activity of the enzyme, (ii) F_o∙F₁ from a number of organisms effectively synthesize, but is unable to hydrolyze ATP, which indicates non-observance of the principle of microreversibility and requires development of a new hypotheses concerning the enzyme mechanism. Since 1980, the group of A. D. Vinogradov has been developing a concept according to which the elementary catalysis stages of ATP hydrolysis and ATP synthesis do not coincide, and there are two independently operating forms of F_o∙F₁ in the coupled membranes – <i>pmf</i>-generating ATPase and <i>pmf</i>-consuming ATP synthase. F_o∙F₁ of <i>P. denitrificans</i> as a natural model of an irreversibly functioning enzyme is a convenient object for experimental verification of the hypothesis of unidirectional energy conversion. The review considers modern concepts of the molecular mechanisms of regulation of F_o∙F₁ ATP synthase/ATPase of <i>P. denitrificans</i> and development of the hypothesis of two forms of F_o∙F₁.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S86 - S104"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moonlighting Proteins of Human and Some Other Eukaryotes. Evolutionary Aspects","authors":"Sergei S. Shishkin","doi":"10.1134/S0006297924602855","DOIUrl":"10.1134/S0006297924602855","url":null,"abstract":"<p>This review presents materials on formation of the concept of moonlighting proteins and general characteristics of different similar proteins. It is noted that the concept under consideration is based on the data on the existence in different organisms of individual genes, protein products of which have not one, but at least two fundamentally different functions, for example, depending on cellular or extracellular location. An important feature of these proteins is that their functions can be switched. As a result, in different cellular compartments or outside the cells, as well as under a number of other circumstances, one of the possible functions can be carried out, and under other conditions, another. It is emphasized that the significant interest in moonlighting proteins is due to the fact that information is currently accumulating about their involvement in many vital molecular processes (glycolysis, translation, transcription, replication, etc.). Alternative hypotheses on the evolutionary origin of moonlighting proteins are discussed.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S36 - S59"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Genome Variants and Alzheimer’s Disease","authors":"Maxim S. Kozin,&nbsp;Olga G. Kulakova,&nbsp;Ivan S. Kiselev,&nbsp;Ekaterina V. Semina,&nbsp;Viktor V. Kakotkin,&nbsp;Mikhail A. Agapov,&nbsp;Olga O. Favorova","doi":"10.1134/S0006297924603174","DOIUrl":"10.1134/S0006297924603174","url":null,"abstract":"<p>Alzheimer’s disease (AD), a severe neurodegenerative disease of the central nervous system, is the most common cause of cognitive impairment in people over the age of 60. The etiology and pathogenesis of Alzheimer’s disease are still unclear despite decades of active research. Numerous studies have shown that neurodegenerative processes in AD are associated with the mitochondrial dysfunction. In this review, we briefly discuss the results of these studies and present the reported evidence that mitochondrial dysfunction in AD is associated with mitochondrial DNA (mtDNA) variations. The results of association analysis of mtDNA haplogroups and individual polymorphic variants, including those whose combinations define haplogroups, with AD are described in detail. These data clearly indicate the role of variations in the mitochondrial genome in the susceptibility to AD, although the problem of significance of individual mtDNA variants is far from being resolved.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S146 - S163"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Virulence of Mycobacterium abscessus and Interaction with the Host Immune System","authors":"Ekaterina V. Zakhareva,&nbsp;Billy A. Martini,&nbsp;Elena G. Salina","doi":"10.1134/S0006297924603496","DOIUrl":"10.1134/S0006297924603496","url":null,"abstract":"<p><i>Mycobacterium abscessus</i> is a non-tuberculosis fast-growing mycobacterium that has recently become a serious concern due to its rapidly increasing prevalence worldwide, mainly in individuals with a high susceptibility to pulmonary infections, for example, patients with cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, and previous tuberculosis infection. According to present estimations, at least 20% of patients with cystic fibrosis are infected with <i>M</i>. <i>abscessus</i>. This bacterium is extremely resistant to most drugs, leading to a severe and difficult-to-treat infection. That is why <i>M. abscessus</i>, previously classified as a low-virulent opportunistic pathogen, is now reconsidered as a true pathogenic bacterium. There are no effective drugs for successful <i>M. abscessus</i> infection therapy, as well as no vaccines to prevent its spread. This review focuses on the molecular mechanisms ensuring <i>M. abscessus</i> resistance to immune response and its ability to survive in the aggressive intracellular environment of human immune cells, and describes virulence factors that can serve as potential targets for the development of innovative therapeutic approaches to combat the spread of infections caused by <i>M. abscessus</i>.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S214 - S232"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Affecting Pathological Amyloid Protein Transformation: From Post-Translational Modifications to Chaperones","authors":"Vladimir I. Muronets,&nbsp;Sofiya S. Kudryavtseva,&nbsp;Lidia P. Kurochkina,&nbsp;Evgeniia V. Leisi,&nbsp;Yulia Yu. Stroylova,&nbsp;Elena V. Schmalhausen","doi":"10.1134/S0006297924604003","DOIUrl":"10.1134/S0006297924604003","url":null,"abstract":"<p>The review discusses the influence of various factors (e.g., post-translational modifications and chaperones) on the pathological transformation of amyloidogenic proteins involved in the onset and development of neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases) and spongiform encephalopathies of various origin with special focus on the role of α-synuclein, prion protein, and, to a lesser extent, beta-amyloid peptide. The factors investigated by the authors of this review are discussed in more detail, including posttranslational modifications (glycation and S-nitrosylation), cinnamic acid derivatives and dendrimers, and chaperonins (eukaryotic, bacterial, and phage). A special section is devoted to the role of the gastrointestinal microbiota in the pathogenesis of amyloid neurodegenerative diseases, in particular, its involvement in the transformation of infectious prions and possibly other proteins capable of prion-like transmission of amyloidogenic diseases.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S164 - S192"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}