Biomedicine & Pharmacotherapy最新文献

{"title":"Linalyl acetate prevents D-galactose and nicotine-induced increases in intracellular Ca2+ by inhibiting phospholipase D hyperactivation in MOVAS and L6 cells","authors":"Yoo Jin Kim ,&nbsp;Jiwoo Shin ,&nbsp;Geun Hee Seol","doi":"10.1016/j.biopha.2025.118538","DOIUrl":"10.1016/j.biopha.2025.118538","url":null,"abstract":"<div><div>Linalyl acetate (LA) is known for its protective effects on vascular and skeletal muscle and for regulating intracellular Ca²⁺ ([Ca²⁺]_i). In this study, we investigated the mechanisms by which nicotine and D-galactose (D-gal) increase [Ca²⁺]_i in vascular smooth muscle cells (MOVAS) and skeletal muscle cells (L6), and examined the protective role of LA. Using a Fura-2 AM–based assay, we found that D-gal+nicotine significantly elevated [Ca²⁺]_i in both cell types, with a greater effect in MOVAS cells. Mechanistically, this abnormal [Ca²⁺]_i increase was mediated through phospholipase D (PLD) hyperactivation in MOVAS cells, while both PLD and phospholipase C (PLC) hyperactivation were involved in L6 cells. In D-gal–treated L6 cells, nicotine further increased [Ca²⁺]_i via additional PLD hyperactivation, suggesting that nicotine exacerbates D-gal–induced Ca²⁺ dysregulation. Treatment with LA effectively rescued these abnormalities by suppressing PLD hyperactivation, thereby restoring [Ca²⁺]_i to normal levels in both cell types. Moreover, our findings indicate that VSMCs are more vulnerable than skeletal muscle cells to D-gal+nicotine–induced [Ca²⁺]_i elevation, likely due to the stronger NCX activation associated with PLD hyperactivation compared to PLC. Taken together, these results demonstrate that D-gal+nicotine induces abnormal Ca²⁺ signaling through PLD hyperactivation, contributing to vascular and skeletal muscle cell stress, and that LA effectively prevents this pathological process. Thus, LA may serve as a promising plant-derived natural compound for preventing cellular aging and Ca²⁺-mediated pathological changes induced by nicotine and D-gal.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118538"},"PeriodicalIF":7.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral nanoformulation of a host-directed antiviral niclosamide effectively treats severe fever with thrombocytopenia syndrome","authors":"Satabdi Acharya ,&nbsp;Hae-mi Kim ,&nbsp;Chongkai Zhai ,&nbsp;Tsenddari Ganbold ,&nbsp;Hyeon Jin Kim ,&nbsp;Seong Tshool Hong","doi":"10.1016/j.biopha.2025.118533","DOIUrl":"10.1016/j.biopha.2025.118533","url":null,"abstract":"<div><div>Severe fever with thrombocytopenia syndrome (SFTS), caused by the tick-borne Dabie bandavirus (DBV), is a serious public health concern due to its high morbidity and mortality rates. However, no antiviral treatment has been developed for SFTS. Through target-focused screening, we identified five anti-SFTS candidates: niclosamide (NIC), cepharanthine, nifedipine, zanamivir, and ivacaftor. Among the 5, NIC showed the highest potency (IC₅₀ = 0.37 μM, CC₅₀ &gt; 50 μM; SI &gt; 135.14). Despite NIC’s strong antiviral activity against DBV, its poor bioavailability limited therapeutic application. To address this, we developed NCNP-NIC, an oral nanoparticle formulation encapsulating NIC with tauroursodeoxycholic acid (TUDCA) via non-covalent interactions. NCNP-NIC formed spherical particles (NIC: TUDCA = 1:4) with an average size of 181 ± 5.02 nm and a polydispersity index of 0.176 ± 0.09. The nanoformulation improved NIC's bioavailability to 52.7 %, a 13-fold increase over pure NIC (4.01 %). As NCNP-NIC involved only non-covalent assembly without new chemical entities, no toxicity was observed. Oral administration of NCNP-NIC at both low (20 mg/kg) and high (40 mg/kg) doses completely cured SFTS in IFNAR−/− mouse model. This work establishes NCNP-NIC as a promising oral therapy for SFTS, while its innovative nanoformulation provides a versatile platform for improving the bioavailability of other poorly soluble antiviral drugs.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118533"},"PeriodicalIF":7.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting protein misfolding in Alzheimer’s disease: The emerging role of molecular chaperones","authors":"Anushka Sharma ,&nbsp;Shriyansh Srivastava ,&nbsp;Pranav Gupta ,&nbsp;Sathvik Belagodu Sridhar ,&nbsp;Mohd. Tariq ,&nbsp;G.S.N. Koteswara Rao ,&nbsp;Sachin Kumar ,&nbsp;Tabarak Malik","doi":"10.1016/j.biopha.2025.118531","DOIUrl":"10.1016/j.biopha.2025.118531","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline and the accumulation of misfolded proteins, including amyloid-beta and hyperphosphorylated tau, which impair neuronal function and promote cell death. These misfolded proteins disrupt proteostasis by forming toxic aggregates that exacerbate disease progression. Molecular chaperones, such as heat shock proteins, actively maintain protein homeostasis by assisting in proper folding, preventing aggregation, and promoting the clearance of misfolded proteins. Dysfunction in chaperone systems contributes to the pathogenesis of AD, positioning them as promising therapeutic targets. Recent research has explored chaperone-based interventions, including small molecules, gene therapies, and autophagy and proteasomal degradation modulators, to restore protein balance. Advances in high-throughput screening and omics technologies have accelerated the identification of potential chaperone modulators. Despite these developments, the complexity of AD and the shortcomings of existing disease models make it difficult to translate preclinical results into successful clinical treatments. This review critically examines the role of protein misfolding and chaperone dysfunction in AD, evaluates emerging therapeutic strategies, and highlights current clinical trials, aiming to bridge molecular mechanisms with translational opportunities in the pursuit of novel AD treatments.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118531"},"PeriodicalIF":7.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dual role of VDAC in cancer: Molecular mechanisms and advances in targeted therapy","authors":"Hongxia Huang,&nbsp;Min Chen,&nbsp;Shubing Feng,&nbsp;Zhenhong Lin,&nbsp;Yuanhang Liu","doi":"10.1016/j.biopha.2025.118530","DOIUrl":"10.1016/j.biopha.2025.118530","url":null,"abstract":"<div><div>The voltage-dependent anion channel (VDAC) family proteins can be subdivided into three isoforms: VDAC1, VDAC2, and VDAC3. As core channels of the mitochondrial outer membrane, these proteins exhibit paradoxical regulatory roles in cancer development. This review systematically summarizes their structural and functional characteristics, as well as the contradictory mechanisms in tumorigenesis and progression.On the one hand, VDAC1 mediates channel closure by binding to the C-terminal tails (CTTs) of tubulins, enhances glycolysis through interaction with hexokinase to promote aerobic glycolysis (Warburg effect), stabilizes mitochondrial membrane potential, inhibits reactive oxygen species (ROS) production, and collaborates with the BNIP3/PINK1-Parkin pathway to regulate mitophagy, thereby facilitating tumor immune escape and metabolic adaptation. On the other hand, tubulin antagonists like erastin induce VDAC1/2 opening to reverse the Warburg effect, killing cancer cells via ferroptosis, and its oligomerization state can reverse apoptotic resistance. Advances in targeted therapy show that compounds based on VDAC gating regulation (such as avicin/acrolein for channel closure and erastin/betulinic acid for channel opening) exhibit significant antitumor effects in models of lung cancer, breast cancer, etc. Moreover, the interaction between TSPO and VDAC, as well as oligomerization regulation mediated by GPCPD1, have emerged as novel strategies.This review highlights the functional heterogeneity of VDAC isoforms and the challenges posed by ROS concentration thresholds for precision therapy, providing a theoretical basis for developing cancer treatment strategies targeting mitochondrial channels.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118530"},"PeriodicalIF":7.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pathogenesis of immune-mediated necrotizing myopathy: Progress and therapeutic implications","authors":"Mengge Yang ,&nbsp;Zhuajin Bi ,&nbsp;Zhijun Li,&nbsp;Jiayang Zhan,&nbsp;Huajie Gao,&nbsp;Qing Zhang,&nbsp;Zhouping Tang,&nbsp;Bitao Bu","doi":"10.1016/j.biopha.2025.118525","DOIUrl":"10.1016/j.biopha.2025.118525","url":null,"abstract":"<div><div>Immune-mediated necrotizing myopathy (IMNM) is an emerging and severe form of myositis. Most patients experience persistent muscle weakness or recurrent attacks within their lifetime. The previous view suggests that autoimmune and complement activation play a key role in muscle damage, and aggressive immunotherapy may benefit patients. However, many patients respond poorly to conventional glucocorticoid and immunosuppressant therapy. Emerging evidence further confirmed the role of anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies in disease development. Autoantibodies may cause muscle damage by internalizing and inhibiting the function of SRP/HMGCR proteins, disturbing protein and lipid metabolism, rather than through a complement-dependent mechanism. Muscle inflammation and activation of the ER stress-autophagy have a dual effect on muscle damage and repair. Moderate activation of these processes helps restore myofiber homeostasis, clear myonecrosis, and regulate regeneration, while excessive activation exacerbates muscle damage. Novel therapies that suppress pathogenic antibody production or accelerate their clearance—such as B-cell depletion therapy, chimeric antigen receptor (CAR) T-cell therapy, BAFF/APRIL inhibitors, and efgartigimod—present great therapeutic potential. A better understanding of IMNM pathogenesis may help clinicians design targeted treatment strategies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118525"},"PeriodicalIF":7.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aurora B inhibition induces polyploidy and mitotic catastrophe in HER2-amplified breast cancer: Telomere shortening as a potential anticancer mechanism of AZD1152-HQPA","authors":"Somayeh Alsadat Tara ,&nbsp;Ali Zekri ,&nbsp;Fattah Sotoodehnejadnematalahi ,&nbsp;Mohammad Hossein Modarressi","doi":"10.1016/j.biopha.2025.118509","DOIUrl":"10.1016/j.biopha.2025.118509","url":null,"abstract":"<div><div>Polyploidy, a conserved mechanism involved in normal development and tissue homeostasis, plays a paradoxical role in cancer by facilitating both tumor progression and therapeutic vulnerability. Although polyploidization may confer survival advantages to cancer cells, its controlled induction could represent an effective anticancer strategy. Aurora B kinase, a critical regulator of mitosis, plays a pivotal role in ensuring chromosomal integrity and preventing polyploidy. However, its role in chromosome ploidy and telomere length maintenance in breast cancer remains insufficiently explored. In this study, we identified a significant association between Aurora B overexpression and poor prognosis exclusively in patients with HER2-amplified breast cancer. Treatment with AZD1152-HQPA, a selective Aurora B kinase inhibitor, significantly reduced cell viability and colony-forming potential, with a pronounced effect on HER2-amplified breast cancer cell lines. Importantly, we found that Aurora B inhibition is sufficient to induce polyploidy/multinucleation (8 N and 16 N), cellular enlargement, and mitotic catastrophe. Furthermore, we observed telomere shortening, downregulation of the human telomerase reverse transcriptase (<em>hTERT</em>) and TERRA (telomeric repeat-containing RNA), and a concomitant increase in ROS production following Aurora B inhibition and polyploidization. Mechanistically, we investigated the protein-protein interaction between Aurora B kinase and upstream regulators of hTERT. Collectively, this study elucidates a novel anticancer mechanism associated with Aurora B inhibition, revealing that AZD1152-HQPA not only impairs mitotic fidelity and promotes polyploidization but also compromises the telomere/telomerase maintenance system. These findings highlight the therapeutic potential of Aurora B inhibitors in targeting telomere-associated vulnerabilities in polyploid cancer cells.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118509"},"PeriodicalIF":7.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal sevoflurane exposure disrupted fatty acids metabolism, leading to hypomyelination and neurological impairments","authors":"Sufang Jiang ,&nbsp;Tianyu Cao ,&nbsp;Jiaqi Li ,&nbsp;Lichao Di ,&nbsp;Xueji Wang ,&nbsp;Zhongcong Xie ,&nbsp;Lining Huang","doi":"10.1016/j.biopha.2025.118495","DOIUrl":"10.1016/j.biopha.2025.118495","url":null,"abstract":"<div><div>Myelin is a lipid-rich substance that is crucial for neural function. Neonatal anesthesia has been linked to neurological impairments associated with myelination dysfunction. This study sought to evaluate whether disrupted fatty acid homeostasis is involved in the mechanism of sevoflurane developmental neurotoxicity. Sevoflurane (3 %, 2 h/day) was administered to mice from postnatal day (P) P6 to P8. Subsequently, ultra-performance liquid chromatography and RNA sequencing (RNA-seq) were used to investigate the effects of sevoflurane on long-chain fatty acid metabolism at P9. Behavioral tests and myelination development were analyzed at P50. Peroxisome proliferator-activated receptor β (PPARβ) agonist administration and docosahexaenoic acid (DHA) treatment were performed to assess their rescuing effect on sevoflurane-impaired cognition in the mice. Following neonatal exposure to sevoflurane, a number of differentially expressed genes (DEGs) were closely related to lipid metabolism. Lipidomic analysis demonstrated that concentrations of long-chain fatty acids were dramatically reduced by repeated sevoflurane exposure. Consistently, cognitive impairments and hypomyelination were observed. Furthermore, the PPARβ agonist KD3010 attenuated the adverse effects of sevoflurane exposure on cognitive function and myelination. DHA treatment mimicked the protective effects of KD3010. These data demonstrate that repeated neonatal sevoflurane exposures result in profound changes in long-chain fatty acids metabolism, hypomyelination and subsequently, neurological impairments. Sevoflurane-induced myelin impairment is associated with changes in fatty acid content and composition, which may be mediated by the PPARβ pathway. These findings highlight the pivotal role of long-chain fatty acids in neonatal sevoflurane-associated neurotoxicity and open a new window for developing therapeutic strategies for sevoflurane-associated neurodevelopmental impairments.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118495"},"PeriodicalIF":7.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular impact of NOTCH signaling dysregulation on ovarian cancer progression, chemoresistance, and taxane response","authors":"Kamila Koucka ,&nbsp;Alzbeta Spalenkova ,&nbsp;Karolina Seborova ,&nbsp;Tereza Tesarova ,&nbsp;Marie Ehrlichova ,&nbsp;Ivona Krus ,&nbsp;Petr Holy ,&nbsp;Lukas Rob ,&nbsp;Martin Hruda ,&nbsp;Jiri Bouda ,&nbsp;Alena Bartakova ,&nbsp;Vendula Smoligova ,&nbsp;Iwao Ojima ,&nbsp;Lei Chen ,&nbsp;Hersch Bendale ,&nbsp;Marcela Mrhalova ,&nbsp;Katerina Kopeckova ,&nbsp;Pavel Soucek ,&nbsp;Radka Vaclavikova","doi":"10.1016/j.biopha.2025.118532","DOIUrl":"10.1016/j.biopha.2025.118532","url":null,"abstract":"<div><div>Patients with epithelial ovarian cancer (EOC) face high mortality due to late diagnosis, recurrence, metastasis, and drug resistance. The NOTCH signaling pathway plays a critical role in cancer progression. This study analyzed NOTCH pathway deregulation in EOC patients and its response to taxane treatment <em>in vitro</em> and <em>in vivo</em>. In tumor cells of EOC patients, a significant upregulation of <em>NOTCH1/3/4</em> and <em>JAG2</em> and a downregulation of the <em>NOTCH2</em> gene were found. The observed high levels of <em>NOTCH3</em> mRNA were also confirmed at the protein level. In contrast, we observed a significant association of low <em>NOTCH4</em> expression with the presence of peritoneal metastasis and shortened platinum-free interval. In the resistant <em>in vitro</em> cell line model, significant upregulation of NOTCH signaling pathway, namely <em>NOTCH3</em>, was observed after treatment with experimental Stony Brook taxanes (SB-Ts), with high efficacy against paclitaxel-resistant ovarian tumor cells. The administration of SB-Ts also caused NOTCH3 upregulation in an effective combination regimen with paclitaxel in comparison to paclitaxel alone and untreated control in the <em>in vivo</em> cell-derived xenograft mouse model of resistant ovarian cancer. Knockdown of the <em>NOTCH3</em> gene caused higher sensitivity of resistant cells to taxanes, suggesting that NOTCH3-specific inhibition may potentially bring therapeutic benefits in resistant ovarian carcinoma. Based on our results, we suggest the <em>NOTCH3</em> gene as a potential target for preclinical studies on resistant ovarian tumors. The current study also highlights the <em>NOTCH4</em> gene as a potential predictive biomarker of therapeutic response in ovarian cancer.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118532"},"PeriodicalIF":7.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of amitriptyline therapy on T cell phenotype in chronic pain patients","authors":"Matthias Hose ,&nbsp;Vivien Blietschau ,&nbsp;Fabian Schumacher ,&nbsp;Anne Ninnemann ,&nbsp;Eyad Naser ,&nbsp;Julia Falkenstein ,&nbsp;Alexander Carpinteiro ,&nbsp;Burkhard Kleuser ,&nbsp;Jan Buer ,&nbsp;Astrid M. Westendorf ,&nbsp;Ulrike Bingel ,&nbsp;Daniel Müller ,&nbsp;Wiebke Hansen","doi":"10.1016/j.biopha.2025.118529","DOIUrl":"10.1016/j.biopha.2025.118529","url":null,"abstract":"<div><div>Chronic pain (CP) is a major health issue globally, affecting millions and resulting in a significant healthcare burden. Although amitriptyline is widely used to manage CP, its immunomodulatory effects during pain therapy, especially on T cell phenotypes, remain unclear. In this study, we explored how amitriptyline alters T cell phenotypes in CP patients. Therefore, we analyzed the expression profile of peripheral T cells from patients suffering from CP before and three months after amitriptyline therapy in comparison to healthy volunteers. Additionally, the impact of amitriptyline on the T cell phenotype was investigated <em>in vitro</em>. Our results revealed that amitriptyline interferes with production of the pro-inflammatory cytokine interferon (IFN)-γ and elevates the anti-inflammatory cytokine interleukin (IL)-10 as well as frequencies of immunosuppressive regulatory T cells, in particular in patients with improved pain after therapy. Hence, amitriptyline therapy affects the adaptive immune response, which might contribute to pain relief through an immune-mediated mechanism.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118529"},"PeriodicalIF":7.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological functions and structural features of Gα12/13 proteins","authors":"Sabriye Aydoğdu,&nbsp;Anna Pepanian,&nbsp;Dhruv C. Rathod,&nbsp;Felina Schulz,&nbsp;Diana Imhof","doi":"10.1016/j.biopha.2025.118523","DOIUrl":"10.1016/j.biopha.2025.118523","url":null,"abstract":"<div><div>Heterotrimeric G proteins are pivotal signal transduction molecules that propagate extracellular signals through G protein-coupled receptors (GPCRs) in the cell. Receptor activation initiates diverse signaling cascades depending on the associated G protein, particularly its Gα subunit, which determines assignment to either the Gαs/olf, Gαi/o, Gαq/11, or Gα12/13 family. The downstream signaling pathways of the families Gαs/olf, Gαi/o, and Gαq/11 have been explored to a greater extent than Gα12/13. The Gα12/13 family interacts with Rho GTPases and thereby regulates physiological functions such as cell migration, cell adhesion, cytoskeletal changes, cell proliferation, transformation, angiogenesis, and embryonic development. Dysregulation and overexpression of this Gα protein family has been implicated in the pathogenesis of disorders such as asthma, cardiovascular diseases, and cancer. In view of the crucial functions, in-depth insights into the signaling pathways and structural properties of the Gα12/13 family are essential for their full characterization and for elucidating their role as potential targets for drug research. This review summarizes the key findings reported so far and emphasizes the importance of a thorough investigation of the Gα12/13 family drawing attention to the lacunae regarding their signaling and structural attributes.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118523"},"PeriodicalIF":7.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}