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The P2X7 purinoceptor in pathogenesis and treatment of dystrophino- and sarcoglycanopathies P2X7嘌呤受体在肌营养不良和肌多糖病的发病机制和治疗中的作用
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-04-01 DOI: 10.1016/j.coph.2023.102357
Dariusz C. Gόrecki, Robin M.H. Rumney
{"title":"The P2X7 purinoceptor in pathogenesis and treatment of dystrophino- and sarcoglycanopathies","authors":"Dariusz C. Gόrecki,&nbsp;Robin M.H. Rumney","doi":"10.1016/j.coph.2023.102357","DOIUrl":"10.1016/j.coph.2023.102357","url":null,"abstract":"<div><p>Dystrophinopathy and sarcoglycanopathies are incurable diseases caused by mutations in the genes encoding dystrophin or members of the dystrophin associated protein complex (DAPC). Restoration of the missing dystrophin or sarcoglycans <em>via</em> genetic approaches is complicated by the downsides of personalised medicines and immune responses against re-expressed proteins. Thus, the targeting of disease mechanisms downstream from the mutant protein has a strong translational potential. Acute muscle damage causes release of large quantities of ATP, which activates P2X7 purinoceptors, resulting in inflammation that clears dead tissues and triggers regeneration. However, in dystrophic muscles, loss of α-sarcoglycan ecto-ATPase activity further elevates extracellular ATP (eATP) levels, exacerbating the pathology. Moreover, seemingly compensatory P2X7 upregulation in dystrophic muscle cells, combined with high eATP leads to further damage. Accordingly, P2X7 blockade alleviated dystrophic damage in mouse models of both dystrophinopathy and sarcoglycanopathy. Existing P2X7 blockers could be re-purposed for the treatment of these highly debilitating diseases.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9497220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Purinergic signalling in graft-versus-host disease 移植物抗宿主病中的嘌呤能信号传导
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102346
Ronald Sluyter , Peter Cuthbertson , Amal Elhage , Chloe Sligar , Debbie Watson
{"title":"Purinergic signalling in graft-versus-host disease","authors":"Ronald Sluyter ,&nbsp;Peter Cuthbertson ,&nbsp;Amal Elhage ,&nbsp;Chloe Sligar ,&nbsp;Debbie Watson","doi":"10.1016/j.coph.2022.102346","DOIUrl":"10.1016/j.coph.2022.102346","url":null,"abstract":"<div><p><span>Allogeneic hematopoietic stem cell<span><span><span> transplantation is used to treat blood cancers, but often results in lethal graft-versus-host disease (GVHD). GVHD is an inflammatory disorder mediated by donor leukocytes that damage host tissues. Purinergic signalling plays important roles in GVHD development in mice but studies of these pathways in human GVHD remain limited. P2X7 receptor activation by ATP on host </span>antigen presenting cells contributes to the induction of GVHD, while activation of this receptor on regulatory </span>T cells, myeloid-derived suppressor cells and possibly type 3 innate lymphoid cells results in their loss to promote GVHD progression. In contrast, A</span></span><sub>2A</sub> receptor activation by adenosine on donor T cells serves to restrict GVHD development. These and other purinergic signalling molecules remain potential biomarkers and therapeutic targets in GVHD.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10834930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
The use of hormone stimulation in male infertility 激素刺激在男性不育中的应用
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102333
Daniel Foran , Runzhi Chen , Channa N. Jayasena , Suks Minhas , Tharu Tharakan
{"title":"The use of hormone stimulation in male infertility","authors":"Daniel Foran ,&nbsp;Runzhi Chen ,&nbsp;Channa N. Jayasena ,&nbsp;Suks Minhas ,&nbsp;Tharu Tharakan","doi":"10.1016/j.coph.2022.102333","DOIUrl":"10.1016/j.coph.2022.102333","url":null,"abstract":"<div><p>Infertility affects 15% of couples worldwide and in approximately 50% of cases the cause is secondary to an abnormality of the sperm. However, treatment options for male infertility are limited and empirical use of hormone stimulation has been utilised. We review the contemporary data regarding the application of hormone stimulation to treat male infertility. There is strong evidence supporting the use of hormone stimulation in hypogonadotropic hypogonadism but there is inadequate evidence for all other indications.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9339915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of extracellular ATP in homeostatic immune cell migration 细胞外ATP在稳态免疫细胞迁移中的作用
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102331
Daichi Kobayashi , Eiji Umemoto , Masayuki Miyasaka
{"title":"The role of extracellular ATP in homeostatic immune cell migration","authors":"Daichi Kobayashi ,&nbsp;Eiji Umemoto ,&nbsp;Masayuki Miyasaka","doi":"10.1016/j.coph.2022.102331","DOIUrl":"10.1016/j.coph.2022.102331","url":null,"abstract":"<div><p>Antigen stimulation induces adenosine triphosphate (ATP) release from naïve lymphocytes in lymphoid tissues. However, previous studies indicated that the non-lytic release of ATP also occurs in most tissues and cell types under physiological conditions. Here, we show that extracellular ATP (eATP) is indeed constitutively produced by naïve T cells in response to lymphoid chemokines in uninflamed lymph nodes and is involved in the regulation of immune cell migration. In this review, we briefly summarize the homeostatic role of extracellular ATP in immune cell migration <em>in vivo</em>.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10834389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Non-hereditary early onset gastric cancer: An unmet medical need 非遗传性早发癌症：未满足的医疗需求
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102344
Angelica Petrillo , Piera Federico , Gianpaolo Marte , Carlo Liguori , Andreas Seeber , Margaret Ottaviano , Andrea Tufo , Bruno Daniele
{"title":"Non-hereditary early onset gastric cancer: An unmet medical need","authors":"Angelica Petrillo ,&nbsp;Piera Federico ,&nbsp;Gianpaolo Marte ,&nbsp;Carlo Liguori ,&nbsp;Andreas Seeber ,&nbsp;Margaret Ottaviano ,&nbsp;Andrea Tufo ,&nbsp;Bruno Daniele","doi":"10.1016/j.coph.2022.102344","DOIUrl":"10.1016/j.coph.2022.102344","url":null,"abstract":"<div><p>Gastric cancer (GC) is a lethal disease and the diagnosis in the young population is a major challenge from both individual and social point of views. Early-onset GC accounts for ∼5% of GC; among them, 3% are part of a hereditary syndrome and the majority are sporadic. However, even if the early-onset forms were less frequent in the past, the increasing number in the last decades has improved the interest and awareness of them in the society and in the scientific community. In particular, the different behaviour and characteristics of early-onset GC suggest that it is a completely different entity, which requires a tailored and personalized management. Here we provide an updated overview about non-hereditary early-onset GC, which is an unmet clinical need today, along with future perspectives in this field.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10834912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Update on anti-fibrotic pharmacotherapies in skeletal muscle disease 骨骼肌疾病抗纤维药物治疗进展
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102332
Laura Muraine, Mona Bensalah, Gillian Butler-Browne, Anne Bigot, Capucine Trollet, Vincent Mouly, Elisa Negroni
{"title":"Update on anti-fibrotic pharmacotherapies in skeletal muscle disease","authors":"Laura Muraine,&nbsp;Mona Bensalah,&nbsp;Gillian Butler-Browne,&nbsp;Anne Bigot,&nbsp;Capucine Trollet,&nbsp;Vincent Mouly,&nbsp;Elisa Negroni","doi":"10.1016/j.coph.2022.102332","DOIUrl":"10.1016/j.coph.2022.102332","url":null,"abstract":"<div><p>Fibrosis, defined as an excessive accumulation of extracellular matrix, is the end point of a defective regenerative process, unresolved inflammation and/or chronic damage. Numerous muscle disorders (MD) are characterized by high levels of fibrosis associated with muscle wasting and weakness. Fibrosis alters muscle homeostasis/regeneration and fiber environment and may interfere with gene and cell therapies. Slowing down or reversing fibrosis is a crucial therapeutic goal to maintain muscle identity in the context of therapies. Several pathways are implicated in the modulation of the fibrotic progression and multiple therapeutic compounds targeting fibrogenic signals have been tested in MDs, mostly in the context of Duchenne Muscular Dystrophy. In this review, we present an up-to-date overview of pharmacotherapies that have been tested to reduce fibrosis in the skeletal muscle.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9339909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Metabolic crosstalk between thermogenic adipocyte and cancer cell: Dysfunction and therapeutics 产热脂肪细胞与癌症细胞之间的代谢串扰：功能障碍与治疗
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102322
Kai Dong , Gang Wei , Honglin Sun , Di Gu , Junli Liu , Linhui Wang
{"title":"Metabolic crosstalk between thermogenic adipocyte and cancer cell: Dysfunction and therapeutics","authors":"Kai Dong ,&nbsp;Gang Wei ,&nbsp;Honglin Sun ,&nbsp;Di Gu ,&nbsp;Junli Liu ,&nbsp;Linhui Wang","doi":"10.1016/j.coph.2022.102322","DOIUrl":"10.1016/j.coph.2022.102322","url":null,"abstract":"<div><p><span>As one of the largest endocrine organs with a wide distribution in organisms, adipose tissue secretes multiple </span>adipokines<span>, cytokines, metabolites, and exosomes to promote tumour development. Elaborating the crosstalk between cancer cells and adipocytes provides a tissue-level perspective of cancer progression, which reflects the heterogeneity and complexity of human tumours. Three main types of adipose tissues, white, brown, and beige adipose tissue, have been described. Thermogenic capacity is a prominent characteristic of brown and beige adipocytes. Most studies so far mainly focus on the contribution of white adipocytes to the tumour microenvironment<span>. However, the role of thermogenic adipose tissue in malignant cancer behaviour has been largely overlooked. Recently, emerging evidence suggests that beige/brown adipocytes play a key role in the development and progression of various cancers. This review focuses on the bidirectional communication between tumour cells and thermogenic adipocytes and the therapeutic strategies to disrupt this interaction.</span></span></p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10773140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Pharmacological strategies for mitigating anti-TNF biologic immunogenicity in rheumatoid arthritis patients 减轻类风湿性关节炎患者抗TNF生物免疫原性的药理学策略。
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102320
Christian A. Fernandez
{"title":"Pharmacological strategies for mitigating anti-TNF biologic immunogenicity in rheumatoid arthritis patients","authors":"Christian A. Fernandez","doi":"10.1016/j.coph.2022.102320","DOIUrl":"10.1016/j.coph.2022.102320","url":null,"abstract":"<div><p><span><span>Tumor necrosis factor alpha<span> (TNFα) inhibitors are a mainstay of treatment for rheumatoid arthritis (RA) patients after failed responses to conventional disease-modifying antirheumatic drugs (DMARDs). Despite the clinical efficacy of TNFα inhibitors (TNFi), many RA patients experience TNFi treatment failure due to the development of anti-drug antibodies (ADAs) that can neutralize drug levels and lead to RA disease relapse. </span></span>Methotrexate (MTX) therapy with concomitant TNFα inhibitors decreases the risk of TNFi </span>immunogenicity<span>, but additional and/or alternative strategies are needed to reduce MTX-associated toxicities and to further increase its potency for preventing TNFα inhibitor immunogenicity. In this review, we highlight the limitations of MTX for mitigating TNFα inhibitor immunogenicity, and we discuss potential alternative pharmacological targets for decreasing the risk of immunogenicity during TNFα inhibitor therapy based on the key kinases, second messengers, and shared signaling mechanisms of lymphocyte receptor signaling.</span></p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540078/pdf/nihms-1931652.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10157351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Drug repurposing in skeletal muscle ion channelopathies 骨骼肌离子通道病的药物再利用
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102329
Concetta Altamura, Ilaria Saltarella, Carmen Campanale, Paola Laghetti, Jean-François Desaphy
{"title":"Drug repurposing in skeletal muscle ion channelopathies","authors":"Concetta Altamura,&nbsp;Ilaria Saltarella,&nbsp;Carmen Campanale,&nbsp;Paola Laghetti,&nbsp;Jean-François Desaphy","doi":"10.1016/j.coph.2022.102329","DOIUrl":"10.1016/j.coph.2022.102329","url":null,"abstract":"<div><p><span><span><span>Skeletal muscle ion channelopathies are rare genetic diseases mainly characterized by </span>myotonia (muscle stiffness) or </span>periodic paralysis (muscle weakness). Here, we reviewed the available therapeutic options in non-dystrophic myotonias (NDM) and periodic paralyses (PP), which consists essentially in </span>drug repositioning<span><span> to address stiffness or weakness attacks. Empirical use followed by successful randomized clinical trials<span><span> eventually led to the orphan drug designation and marketing authorization granting of </span>mexiletine for NDM and </span></span>dichlorphenamide<span> for PP. Yet, these treatments neither consider the genetic cause of the diseases nor address the individual variability in drug response. Thus, ongoing research aims at the identification of repurposed drugs alternative to mexiletine and dichlorphenamide to allow personalization of treatment. This review highlights how drug repurposing may represent an efficient strategy in rare diseases, allowing reduction of drug development time and costs in a context in which the return on investment may be particularly challenging.</span></span></p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9324632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Three-dimensional perspective on ryanodine receptor mutations causing skeletal and cardiac muscle-related diseases ryanodine受体突变引起骨骼肌和心肌相关疾病的三维视角
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-02-01 DOI: 10.1016/j.coph.2022.102327
Kavita A. Iyer, Vadim Barnakov, Montserrat Samsó
{"title":"Three-dimensional perspective on ryanodine receptor mutations causing skeletal and cardiac muscle-related diseases","authors":"Kavita A. Iyer,&nbsp;Vadim Barnakov,&nbsp;Montserrat Samsó","doi":"10.1016/j.coph.2022.102327","DOIUrl":"10.1016/j.coph.2022.102327","url":null,"abstract":"<div><p>Mutations in RyR alter the cell's Ca<sup>2+</sup><span> homeostasis and can cause serious health problems for which few effective therapies are available. Until recently, there was little structural context for the hundreds of mutations linked to muscular disorders reported for this large channel. Growing knowledge of the three-dimensional structure of RyR starts to illustrate the fine control of Ca</span><sup>2+</sup> release. Current efforts directed towards understanding how disease mutations impinge in such processes will be crucial for future design of novel therapies. In this review article we discuss the up-to-date information about mutations according to their role in the 3D structure, and classified them to provide context from a structural perspective.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10776325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
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