Biochemistry (Moscow)最新文献

{"title":"Accumulation Dynamics of Various Proteasome Forms in Colorectal Adenocarcinoma Cells Treated with Interferon-Gamma","authors":"Alexey V. Morozov,&nbsp;Anastasia Yu. Kravchenko,&nbsp;Alesya M. Mikheeva,&nbsp;Vladimir I. Popenko,&nbsp;Olga G. Leonova,&nbsp;Vladimir S. Prassolov,&nbsp;Timofey D. Lebedev,&nbsp;Vadim L. Karpov","doi":"10.1134/S0006297926602030","DOIUrl":"10.1134/S0006297926602030","url":null,"abstract":"<p>Most intracellular proteins are degraded by proteasomes. In addition to constitutive proteasomes (cPs), cells form non-constitutive proteasomes (ncPs), which contain alternative catalytic subunits. These proteasomes play a key role in immunological reactions and cellular response to stress. The ncPs synthesis is activated by interferon-γ (IFN-γ), however, studies of the proteasome pool dynamics following IFN-γ treatment have not been conducted with high temporal resolution and visualization of cPs and ncPs in the same cells. To characterize accumulation of proteasome subunits, two-dimensional (2D) and three-dimensional (3D) cultures of a human colorectal adenocarcinoma reporter cell line expressing the fluorescently tagged cP subunit β5 and ncP subunit β5i were used. The expression of proteasome subunits in 2D cell culture was assessed using real-time PCR, Western blotting, flow cytometry, fluorescence microscopy, and automated fluorescence microscopy after treatment with IFN-γ for 2, 4, 8, 10, 24, 28, 32, 48, 52, 56, and 72 h. The incorporation of subunits into proteasomes was studied by Western blotting and an activity-based probe. In parallel, changes in tumor spheroid fluorescence were examined 24, 48, and 72 h after the start of IFN-γ treatment. In 2D culture, increased levels of mRNA of ncP subunits were detected after 4 h of incubation with the cytokine. Accumulation and incorporation of ncP subunits into proteasomes were observed following 8 h of incubation, reaching maximum at 56-72 h post IFN-γ administration. Notably, starting from 48 h, a decrease in the amount of cP subunit β5 was detected within cells. In 3D models, significant changes in spheroid fluorescence occurred only after 48 h of incubation with IFN-γ. However, at the periphery of treated spheroids, the β5i subunit expression began to increase after 24 h, indicating delayed cytokine penetration into the spheroid interior. These results clarify the dynamics of IFN-γ-induced proteasome pool reorganization. The obtained data can be used to analyze the effects of drugs and modify IFN-γ-based treatment protocols.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1673 - 1689"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098398","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":"What Is the Role of Cohesin in Transcription Regulation?","authors":"Sergey V. Ulianov,&nbsp;Sergey V. Razin","doi":"10.1134/S0006297926602285","DOIUrl":"10.1134/S0006297926602285","url":null,"abstract":"<p>Available experimental data do not yet permit an unambiguous or comprehensive answer to the question posed in the title. A conventional approach to determining the role of a particular protein in cellular processes is to remove or inactivate it. However, transcriptome analyses following cohesin depletion have yielded markedly different results depending on the used experimental strategy, including conditional genetic knockout, RNA interference, and rapid inducible degradation systems. From a historical perspective, we examined why, until the mid-2010s, cohesin had been widely regarded as a major regulator of transcription and why later, this conclusion could no longer be maintained with the same degree of certainty. Recent observations suggest that a coherent understanding of cohesin’s role in transcriptional regulation may emerge from two complementary developments: the recent discovery of new classes of genomic elements and detailed analyses of the genetic architecture of individual loci exhibiting distinct responses to cohesin depletion or to inhibition of cohesin-mediated extrusion.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1550 - 1565"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098210","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":"DNA Methylation of the SNCA Intron 1 and Alpha-Synuclein Expression in the CD45+ Blood Cells in Parkinson’s Disease","authors":"Anna O. Lavrinova,&nbsp;Ekaterina M. Litusova,&nbsp;Alexey A. Dmitriev,&nbsp;Nataliya V. Melnikova,&nbsp;Victoria N. Pidyurchina,&nbsp;Darya G. Kulabukhova,&nbsp;Olesya V. Syreva,&nbsp;Irina V. Miliukhina,&nbsp;Alla A. Timofeeva,&nbsp;Olga A. Berkovich,&nbsp;Sofya N. Pchelina,&nbsp;Anton K. Emelyanov","doi":"10.1134/S0006297926601735","DOIUrl":"10.1134/S0006297926601735","url":null,"abstract":"<p>Alpha-synuclein oligomers are believed to be the major neurotoxic agents in neurodegenerative process in Parkinson’s disease (PD). The <i>SNCA</i> gene expression has been shown to be regulated by methylation of the <i>SNCA</i> intron 1. Polymorphisms in the <i>SNCA</i> promoter and 3′-untranslated regions could affect the <i>SNCA</i> gene expression and gene methylation. The study included 46 L-DOPA-naïve sporadic PD (sPD) patients and 64 individuals in the control group. We evaluated methylation of the <i>SNCA</i> intron 1 in the CD45+ blood cells along with the <i>SNCA</i> expression (mRNA, protein) in the sPD patients and controls. Negative correlations were found between the levels of DNA methylation of all of 23 CpG sites and of individual CpG sites in the <i>SNCA</i> intron 1 and the levels of alpha-synuclein expression (mRNA and protein) in the controls. No difference in the methylation of the <i>SNCA </i>intron 1 in the CD45+ blood cells between the PD patients and controls was found. However, hypermethylation of the CpG site at position 22 in the intron 1 of the <i>SNCA</i> gene in the sPD patients was revealed. It was found that the rs3756063 <i>SNCA</i> genotype influence the <i>SNCA</i> intron 1 methylation level in the CD45+ blood cells both in the sPD patients and controls. Influence of the rs3756063 <i>SNCA</i> genotypes on the alpha-synuclein levels in the CD45+ blood cells was found in the group of sPD patients. Therefore, our data demonstrated that methylation of the <i>SNCA</i> intron 1 is associated with the alpha-synuclein expression levels in the CD45+ blood cells in the controls, but methylation status does not differ between the sPD patients and controls. The obtained results confirmed the effect of rs3756063 polymorphism on methylation of the <i>SNCA</i> intron 1 in the CD45+ blood cells.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1629 - 1643"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098213","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":"Astrocyte Structure–Function Relationship in Senescence and Neurodegeneration","authors":"Daria V. Serebryanaya,&nbsp;Ksenia A. Kolgaeva,&nbsp;German A. Dya,&nbsp;Ivan M. Ermakov,&nbsp;Vsevolod V. Belousov","doi":"10.1134/S000629792660208X","DOIUrl":"10.1134/S000629792660208X","url":null,"abstract":"<p>Astrocytes play a critical role in maintaining brain homeostasis by providing metabolic support to neurons, regulating neurotransmitter levels, modulating synaptic transmission, and preserving the blood–brain barrier (BBB) integrity. Aging is associated with the accumulation of senescent astrocytes – cells that have lost their ability to grow and divide but remained metabolically active and resistant to apoptosis. In neurodegenerative diseases, astrocytes develop a reactive phenotype. Both senescent and reactive astrocytes are characterized by distinct secretory phenotypes known for the production of pro-inflammatory cytokines, chemokines, and metalloproteinases, that considerably overlap in both states of astrocytes. Recent studies indicate that the number of senescent astrocytes in the brain directly correlates with the development of neurodegenerative diseases. However, the relationship between senescence and neurodegeneration remains poorly understood. This review examines the similarities and differences in the structural and functional features of astrocytes in senescent and pro-inflammatory states, explores potential interactions between them, analyzes intermediate functional states, and discusses potential mechanisms by which astrocytes of both phenotypes contribute to the development of neurodegenerative diseases.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1522 - 1549"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098215","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":"Oligomerization of the Recombinant CD40L Increases Its Agonist Activity upon Stimulation of Human B Cells","authors":"Artem A. Mikhailov,&nbsp;Maria G. Byazrova,&nbsp;Maria M. Sukhova,&nbsp;Maxim V. Petukhov,&nbsp;Eleonora V. Shtykova,&nbsp;Alexander V. Filatov","doi":"10.1134/S0006297926602133","DOIUrl":"10.1134/S0006297926602133","url":null,"abstract":"<p>The CD40L molecule is primarily expressed on the activated CD4⁺ T lymphocytes and plays a key role in the immune response. Upon contact with a B lymphocyte, CD40L binds to the CD40 receptor and triggers signaling pathways, leading to B cell proliferation and differentiation and inducing a switch in Ig synthesis. When using soluble forms of CD40L as an activator, preliminary forced multimerization of CD40L is a prerequisite. A construct in which the receptor-binding domain of CD40L is fused to the collagen-like domain of adiponectin (Adn) is often used to multimerize CD40L. It is believed that Adn-CD40L forms several oligomeric forms. In our study, we obtained an Adn-CD40L preparation from which we isolated the low-molecular-weight and high-molecular-weight forms of Adn-CD40L (LMW and HMW). We next studied their biochemical, structural, and functional characteristics. It was concluded that LMW is a trimer of Adn-CD40L, while HMW is a mixture of higher-order oligomers. LMW demonstrated higher activity in the NF-κB-dependent signaling pathway activation assays compared to HMW. However, HMW induced more pronounced B-cell expansion and stimulated Ig secretion to a greater extent than LMW. These results could be used to develop new CD40L-based immunotherapeutics.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1690 - 1703"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098399","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":"Comparison of the Properties of PARP1 and HPF1 in Naked Mole-Rat and Human","authors":"Kirill D. Nazarov,&nbsp;Alexey A. Popov,&nbsp;Konstantin N. Naumenko,&nbsp;Artem R. Nurislamov,&nbsp;Egor O. Ukladov,&nbsp;Veniamin S. Fishman,&nbsp;Irina O. Petruseva,&nbsp;Olga I. Lavrik","doi":"10.1134/S0006297925602667","DOIUrl":"10.1134/S0006297925602667","url":null,"abstract":"<p>DNA repair is the main mechanism for maintaining genome stability in living organisms and is considered one of the key factors influencing the maximum lifespan of mammals. Two proteins are of particular interest in the context of studying molecular basis of longevity: the key DNA repair regulator poly(ADP-ribose) polymerase 1 (PARP1) and the recently discovered modulator of its activity, histone poly(ADP-ribosyl)ation factor 1 (HPF1). This work analyzes the results of comparative analysis of the primary structures of PARP1 and HPF1, as well as examples of computer modeling of the orthologous proteins PARP1 and HPF1 and their complexes. As part of comparative assessment of the properties of recombinant PARP1 and HPF1 from two long-lived mammals, the naked mole-rat and human, we compared their amino acid sequences, stability of these protein structures under the action of denaturing agents, strength of the PARP1 ortholog complexes with DNA, effect of the recombinant HPF1 proteins on PARP1 automodification, and the results of 3D modeling of the PARP1–HPF1 complexes. Despite the differences in primary structures, the naked mole-rat and human PARP1 exhibited similar kinetic parameters in the poly(ADP-ribosyl)ation reaction catalyzed by these enzymes, as well as similar levels of stability of the complexes formed by the PARP1 orthologs with a DNA duplex. Due to predominantly hydrophobic nature of amino acid substitutions in the PARP1 sequence, the naked mole-rat PARP1 proved to be more thermostable and resistant to the denaturing effect of urea, whereas differences in the primary structures of the HPF1 orthologs did not result in any difference in their stability. At the same time, both HPF1 proteins (homologous and heterologous) stimulated human PARP1 in the auto-poly(ADP-ribosyl)ation reaction with comparable efficiency. We suggest that the observed effects are associated with the differences in the primary structures of PARP1 proteins. The obtained results may serve as a foundation for further comparative studies of the properties of PARP family proteins in both naked mole-rats and humans, as well as in other mammals.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1660 - 1672"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098401","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":"NAD and NADPH in Neuronal Injury and Degeneration","authors":"Svyatoslav S. Savin,&nbsp;Denis L. Atroshenko,&nbsp;Tatyana A. Chubar,&nbsp;Anastasia A. Pometun,&nbsp;Dmitry M. Hushpulian,&nbsp;Sergey V. Nikulin,&nbsp;Bobby Thomas,&nbsp;Gabriel M. Kazakov,&nbsp;Abraham M. Brown,&nbsp;Richard J. Zeman,&nbsp;Irina G. Gazaryan,&nbsp;Natalia L. Klyachko","doi":"10.1134/S0006297926603229","DOIUrl":"10.1134/S0006297926603229","url":null,"abstract":"<p>The review focuses on novel targets recently identified in the mechanisms of neuronal death, and specifically in axonal degeneration. Depletion of NAD triggers various death pathways depending on the nature of the NAD degradation trigger. Wallerian degeneration (WD) of axons in the peripheral nervous system follows the specific mechanism activated by NMNAT2/SARM1 – “sarmoptosis”, which is also observed in other tissues, and contributes to the chemotherapy-induced neurological effects. An allosteric inhibitor of the NADase activity of SARM1, SIR2501, has been recently approved by FDA for prevention of chemotherapy-induced peripheral neuropathy. Sarmoptosis cross-talks to apoptosis and ferroptosis in the injury-induced axonal degeneration of the central nervous system and, in particular, in spinal cord injury. NADPH plays opposing roles in the cell death. Ferroptosis suppressor protein 1 (FSP1), an NADPH-dependent enzyme, is the key actor generating ubiquinol Q10 to neutralize lipid peroxides. On the other hand, NOX4 activation results in ROS generation from NADPH. NADPH depletion through the polyol pathway activation diminishes antioxidant capacity of the cell and sends pro-death signal through the NADPH sensor in ER – ubiquitin ligase MARCHF6 (Membrane Associated Ring-CH-Type Finger 6). Under the conditions of low NADPH concentrations, MARCHF6 stabilizes pro-death proteins such as p53 and ferroptosis-fueling enzyme ACSL4 (Acyl-CoA synthetase long-chain family member 4). Under the conditions of high NADPH concentration, MARCHF6 ubiquitinates p53 and ACSL4 targeting them for the proteasomal degradation. Regulation of MARCHF6 activity is a promising target for intervention; however, no small molecules mimicking NADPH effect are currently available. In conclusion, the review discusses to what extent the existing NAD supplements could perform the role of targeted medicines.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1507 - 1521"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098214","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":"mTOR and STING Modulation Restores Hydrolase Activities and Decreases Alpha-Synuclein Pathology in the Cells from the Patients with GBA1-Associated Parkinson’s Disease","authors":"Tatiana S. Usenko,&nbsp;Anastasia I. Bezrukova,&nbsp;Katerina S. Basharova,&nbsp;Elena V. Grigor’eva,&nbsp;Sofya V. Pavlova,&nbsp;Galina V. Baydakova,&nbsp;Irina V. Miliukhina,&nbsp;Ekaterina Yu. Zakharova,&nbsp;Sofya N. Pchelina","doi":"10.1134/S0006297926601644","DOIUrl":"10.1134/S0006297926601644","url":null,"abstract":"<p>Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and pathological accumulation of alpha-synuclein. Aberrant activation of the mechanistic target of rapamycin (mTOR) and of the stimulator of interferon genes (STING) signaling pathways are increasingly recognized as central contributors to PD pathogenesis. The <i>GBA1</i> variants are the most common genetic risk factor for PD. However, currently there are no disease-modifying therapies for treatment of the GBA1-associated PD (GBA1-PD). Here, we investigated the effects of selective inhibitors of mTOR (Torin 1) and STING (H-151) on the pathway activity, autophagy, lysosomal function, including hydrolase activity, and lysosphingolipid levels, in the peripheral blood monocyte cells-derived macrophages (PBMC-derived macrophages) and induced pluripotent stem cell (iPSC)-derived dopaminergic neurons from the patients with GBA1-PD. Consistent with our previous findings of the reduced glucocerebrosidase (GCase) activity, substrate accumulation, and impaired autophagy, the cells derived from the GBA1-PD patients exhibited marked activation of both mTOR and STING signaling. mTOR inhibition increased number and size of lysosomes and reduced the level of monomeric alpha-synuclein, consistent with the enhanced TFEB-mediated lysosomal biogenesis. In contrast, STING inhibition broadly attenuated the disease-associated phenotypes, reducing levels of oligomeric and phosphorylated alpha-synuclein (Ser129), lysosphingolipid accumulation, and Ras-related protein Rab-10 (Rab10) phosphorylation (Thr73), while also decreasing TFEB phosphorylation, which is consistent with TFEB activation and restoration of lysosomal trafficking via the LRRK2-dependent mechanism. Together, these findings identify mTOR and STING as central regulators of lysosomal functioning and GCase activity in the GBA1-PD, acting through the distinct but partially overlapping mechanisms. Targeting these pathways could, therefore, provide a strategy to restore lysosomal homeostasis and autophagic flux, either alone or in combination with other therapeutic approaches, and to mitigate the alpha-synuclein pathology in GBA1-PD.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1596 - 1614"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098226","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":"Newly Identified FDA-Approved MTAs: Opportunities for Antimicrobial Repurposing?","authors":"Amira Zhor Rim Zinai,&nbsp;Mapenda Gaye,&nbsp;Viktoriia E. Baksheeva,&nbsp;Florence Fenollar,&nbsp;Philipp O. Tsvetkov,&nbsp;Oleg Mediannikov","doi":"10.1134/S0006297926601504","DOIUrl":"10.1134/S0006297926601504","url":null,"abstract":"<p>The emergence of antimicrobial resistance represents a major global health challenge, highlighting the urgent need for new therapeutic strategies. Drug repurposing, particularly through the evaluation of FDA-approved compounds with well-established pharmacological profiles, offers a promising avenue. In this study, we performed a phenotypic screening of 31 FDA-approved compounds recently identified as potent Microtubule-Targeting Agents (MTAs) to evaluate their antimicrobial potential. Using agar well diffusion assays, we tested these compounds against selected human pathogenic bacterial and fungal strains. Our results provide the first evidence that several MTAs possess previously unrecognized antimicrobial activities. Of the 31 compounds screened, 18 exhibited inhibitory effects against at least one bacterial or fungal strain, identifying MTAs as potential antimicrobial leads for further investigation. Notably, auranofin, a gold-based antirheumatic agent, consistently displayed antimicrobial activity across all tested strains. Flupentixol dihydrochloride demonstrated selective antifungal inhibition, while mefloquine hydrochloride showed broad-spectrum antibacterial effects. These findings suggest that anti-tubulin activity may contribute to the antifungal effects observed, whereas the possible involvement of FtsZ in the antibacterial activity remains speculative. Further studies, including minimum inhibitory concentration (MIC) determinations, cytotoxicity and selectivity assessments, and mechanistic analyses, are needed to validate these findings and evaluate their potential for antimicrobial repurposing.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1587 - 1595"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098209","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":"Induction of the Full-Length FoxP3 Splice Variant during ex vivo Transformation of Human CD4+ T Lymphocytes into Regulatory T Cells","authors":"Varvara G. Blinova,&nbsp;Yulia A. Gladilina,&nbsp;Anastasiya N. Shishparenok,&nbsp;Daria D. Eliseeva,&nbsp;Dmitry D. Zhdanov","doi":"10.1134/S0006297926601954","DOIUrl":"10.1134/S0006297926601954","url":null,"abstract":"<p>Regulatory T cells (Tregs) control immune responses to autoantigens and play a key role in suppressing autoimmune reactions during the development of autoimmune diseases. One of the approaches to personalized regenerative therapy for autoimmune diseases is enhancing the proliferative and suppressive activities of Tregs <i>ex vivo</i>. The transcription factor Forkhead box protein P3 (FoxP3) is a key regulator of the proliferative and suppressive activities of Tregs. FoxP3 pre-mRNA undergoes alternative splicing, and the full-length splice variant stimulates Treg proliferation and suppressive activity. In this study, we used cells obtained from three healthy donors and three patients with multiple sclerosis to compared the levels of FoxP3 splice variants in Tregs during their <i>ex vivo</i> expansion (expanded Tregs, eTregs) and Tregs generated by transformation of CD4⁺ T cells (transformed Tregs, tTregs). The full-length FoxP3 splice variant predominated in tTregs during the transformation process, which was accompanied by the increased proliferative and suppressive activities of these cells. In contrast, <i>ex vivo</i> expansion of eTregs did not alter the proportions of FoxP3 splice variants; these cells proliferated less actively and exhibited lower suppressive activity than tTregs. Our findings demonstrate that transformation of CD4⁺ T cells into Tregs is accompanied by an increase in the proportion of the full-length FoxP3 splice variant. Therefore, transformation may represent a more effective strategy than expansion of mature Tregs for generation of highly proliferative and suppressive cells in regenerative medicine.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1644 - 1659"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098397","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}