Expert Opinion on Therapeutic Targets最新文献

{"title":"Combining rejuvenation interventions in rodents: a milestone in biomedical gerontology whose time has come.","authors":"Caitlin J Lewis, Aubrey D de Grey","doi":"10.1080/14728222.2024.2330425","DOIUrl":"10.1080/14728222.2024.2330425","url":null,"abstract":"<p><strong>Introduction: </strong>Longevity research has matured to the point where significantly postponing age-related decline in physical and mental function is now achievable in the laboratory and foreseeable in the clinic. The most promising strategies involve rejuvenation, i.e. reducing biological age, not merely slowing its progression.</p><p><strong>Areas covered: </strong>We discuss therapeutic strategies for rejuvenation and results achieved thus far, with a focus on in vivo studies. We discuss the implications of interventions which act on mean or maximum lifespan and those showing effects in accelerated disease models. While the focus is on work conducted in mice, we also highlight notable insights in the field from studies in other model organisms.</p><p><strong>Expert opinion: </strong>Rejuvenation was originally proposed as easier than slowing aging because it targets initially inert changes to tissue structure and composition, rather than trying to disentangle processes that both create aging damage and maintain life. While recent studies support this hypothesis, a true test requires a panel of rejuvenation interventions targeting multiple damage categories simultaneously. Considerations of cost, profitability, and academic significance have dampened enthusiasm for such work, but it is vital. Now is the time for the field to take this key step toward the medical control of aging.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109779","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":"Leveraging AI to identify dual-purpose aging and disease targets.","authors":"Geoffrey Ho Duen Leung, Chun Wai Wong, Frank W Pun, Alex Aliper, Feng Ren, Alex Zhavoronkov","doi":"10.1080/14728222.2023.2288270","DOIUrl":"10.1080/14728222.2023.2288270","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458850","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 inflammasome complexes as a novel therapeutic strategy for mood disorders.","authors":"Aline Silva de Miranda, Eliana Cristina de Brito Toscano, Jason C O'Connor, Antonio Lucio Teixeira","doi":"10.1080/14728222.2024.2366872","DOIUrl":"10.1080/14728222.2024.2366872","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammasome complexes, especially NLRP3, have gained great attention as a potential therapeutic target in mood disorders. NLRP3 triggers a caspase 1-dependent release of the inflammatory cytokines IL-1β and IL-18, and seems to interact with purinergic and kynurenine pathways, all of which are implicated in mood disorders development and progression.</p><p><strong>Areas covered: </strong>Emerging evidence supports NLRP3 inflammasome as a promising pharmacological target for mood disorders. We discussed the available evidence from animal models and human studies and provided a reflection on drawbacks and perspectives for this novel target.</p><p><strong>Expert opinion: </strong>Several studies have supported the involvement of NLRP3 inflammasome in MDD. However, most of the evidence comes from animal models. The role of NLRP3 inflammasome in BD as well as its anti-manic properties is not very clear and requires further exploration. There is evidence of anti-manic effects of P2×R7 antagonists associated with reduction in the brain levels of IL-1β and TNF-α in a murine model of mania. The involvement of other NLRP3 inflammasome expressing cells besides microglia, like astrocytes, and of other inflammasome complexes in mood disorders also deserves further investigation. Preclinical and clinical characterization of NLRP3 and other inflammasomes in mood disorders is needed before considering translational approaches, including clinical trials.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317232","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 role of collagen triple helix repeat containing 1 (CTHRC1) in cancer development and progression.","authors":"Chandra K Singh, Sofia Fernandez, Gagan Chhabra, Gabriella R Zaemisch, Ayaan Nihal, Jenna Swanlund, Naveed Ansari, Zan Said, Hao Chang, Nihal Ahmad","doi":"10.1080/14728222.2024.2349686","DOIUrl":"10.1080/14728222.2024.2349686","url":null,"abstract":"<p><strong>Introduction: </strong>Collagen triple helix repeat containing 1 (CTHRC1) is a protein that has been implicated in pro-migratory pathways, arterial tissue-repair processes, and inhibition of collagen deposition via the regulation of multiple signaling cascades. Studies have also demonstrated an upregulation of CTHRC1 in multiple cancers where it has been linked to enhanced proliferation, invasion, and metastasis. However, the understanding of the exact role and mechanisms of CTHRC1 in cancer is far from complete.</p><p><strong>Areas covered: </strong>This review focuses on analyzing the role of CTHRC1 in cancer as well as its associations with clinicopathologies and cancer-related processes and signaling. We have also summarized the available literature information regarding the role of CTHRC1 in tumor microenvironment and immune signaling. Finally, we have discussed the mechanisms associated with CTHRC1 regulations, and opportunities and challenges regarding the development of CTHRC1 as a potential target for cancer management.</p><p><strong>Expert opinion: </strong>CTHRC1 is a multifaceted protein with critical roles in cancer progression and other pathological conditions. Its association with lower overall survival in various cancers, and impact on the tumor immune microenvironment make it an intriguing target for further research and potential therapeutic interventions in cancer.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty liver disease: time to target CCR5?","authors":"Vlad Dumitru Brata, Frank Tacke","doi":"10.1080/14728222.2024.2366880","DOIUrl":"10.1080/14728222.2024.2366880","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300470","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 HIF-1α in sickle cell disease and cancer: unraveling therapeutic opportunities and risks.","authors":"Saba Ubaid, Mohammad Kashif, Yusra Laiq, Akshay Kumar Nayak, Vipin Kumar, Vivek Singh","doi":"10.1080/14728222.2024.2367640","DOIUrl":"10.1080/14728222.2024.2367640","url":null,"abstract":"<p><strong>Introduction: </strong>HIF-1α, a key player in medical science, holds immense significance in therapeutic approaches. This review delves into its complex dynamics, emphasizing the delicate balance required for its modulation. HIF-1α stands as a cornerstone in medical research, its role extending to therapeutic strategies. This review explores the intricate interplay surrounding HIF-1α, highlighting its critical involvement and the necessity for cautious modulation.</p><p><strong>Areas covered: </strong>In sickle cell disease (SCD), HIF-1α's potential to augment fetal hemoglobin (HbF) production and mitigate symptoms is underscored. Furthermore, its role in cancer is examined, particularly its influence on survival in hypoxic tumor microenvironments, angiogenesis, and metastasis. The discussion extends to the intricate relationship between HIF-1α modulation and cancer risks in SCD patients, emphasizing the importance of balancing therapeutic benefits and potential hazards.</p><p><strong>Expert opinion: </strong>Managing HIF-1α modulation in SCD patients requires a nuanced approach, considering therapeutic potential alongside associated risks, especially in exacerbating cancer risks. An evolutionary perspective adds depth, highlighting adaptations in populations adapted to low-oxygen environments and aligning cancer cell metabolism with primitive cells. The role of HIF-1α as a therapeutic target is discussed within the context of complex cancer biology and metabolism, acknowledging varied responses across diverse cancers influenced by intricate evolutionary adaptations.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300471","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":"Current challenges in the discovery of treatments against Mayaro fever.","authors":"Rafael Elias Marques, Jacqueline Farinha Shimizu, Maurício Lacerda Nogueira, Nikos Vasilakis","doi":"10.1080/14728222.2024.2351504","DOIUrl":"10.1080/14728222.2024.2351504","url":null,"abstract":"<p><strong>Introduction: </strong>Mayaro fever is an emerging viral disease that manifests as an acute febrile illness. The disease is self-limiting, however joint pain can persist for months leading to chronic arthralgia. There is no specific treatment available, which ultimately leads to socioeconomic losses in populations at risk as well as strains to the public health systems.</p><p><strong>Areas covered: </strong>We reviewed the candidate treatments proposed for Mayaro virus (MAYV) infection and disease, including antiviral compounds targeting viral or host mechanisms, and pathways involved in disease development and pathogenicity. We assessed compound screening technologies and experimental infection models used in these studies and indicated the advantages and limitations of available technologies and intended therapeutic strategies.</p><p><strong>Expert opinion: </strong>Although several compounds have been suggested as candidate treatments against MAYV infection, notably those with antiviral activity, most compounds were assessed only <i>in vitro</i>. Compounds rarely progress to<i>in vivo</i> or preclinical studies, and such difficulty may be associated with limited experimental models. MAYV biology is largely inferred from related alphaviruses and reflected by few studies focusing on target proteins or mechanisms of action for MAYV. Therapeutic strategies targeting pathogenic inflammatory responses have shown potential against MAYV-induced disease <i>in vivo</i>, which might reduce long-term sequelae.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV Pol: does it offer therapeutic targets for HIV?","authors":"Camilla Muccini, Antonella Castagna","doi":"10.1080/14728222.2024.2351510","DOIUrl":"10.1080/14728222.2024.2351510","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863429","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":"Novel benzimidazole angiotensin receptor blockers with anti-SARS-CoV-2 activity equipotent to that of nirmatrelvir: computational and enzymatic studies.","authors":"Harry Ridgway, Graham J Moore, Laura Kate Gadanec, Anthony Zulli, Vasso Apostolopoulos, Weronika Hoffmann, Katarzyna Węgrzyn, Niki Vassilaki, George Mpekoulis, Marios Zouridakis, Petros Giastas, Veroniki P Vidali, Konstantinos Kelaidonis, Minos-Timotheos Matsoukas, Marios Dimitriou, Thomas Mavromoustakos, Sotirios Tsiodras, Vassilis G Gorgoulis, Ioannis Karakasiliotis, Christos T Chasapis, John M Matsoukas","doi":"10.1080/14728222.2024.2362675","DOIUrl":"10.1080/14728222.2024.2362675","url":null,"abstract":"<p><strong>Background: </strong>Hypertension worsens outcomes in SARS-CoV-2 patients. Sartans, a type of antihypertensive angiotensin receptor blocker-(ARB), reduce COVID-19 morbidity and mortality by targeting angiotensin-converting enzyme-2 (ACE2). This study aimed to evaluate the antiviral and antihypertensive effects of nirmatrelvir, commercial sartans (candesartan, losartan, and losartan carboxylic (Exp3174)), and newly synthesized sartans (benzimidazole-N-biphenyl carboxyl (ACC519C) and benzimidazole-N-biphenyl tetrazole (ACC519T)), compared to nirmatrelvir, the antiviral component of Paxlovid.</p><p><strong>Research design and methods: </strong>Surface plasmon resonance (SPR) and enzymatic studies assessed drug effects on ACE2. Antiviral abilities were tested with SARS-CoV-2-infected Vero E6 cells, and antihypertensive effects were evaluated using angiotensin II-contracted rabbit iliac arteries.</p><p><strong>Results: </strong>Benzimidazole-based candesartan and ACC519C showed antiviral activity comparable to nirmatrelvir (95% inhibition). Imidazole-based losartan, Exp3174, and ACC519T were less potent (75%-80% and 50%, respectively), with Exp3174 being the least effective. SPR analysis indicated high sartans-ACE2 binding affinity. Candesartan and nirmatrelvir combined had greater inhibitory and cytopathic effects (3.96%) than individually (6.10% and 5.08%). ACE2 enzymatic assays showed varying effects of novel sartans on ACE2. ACC519T significantly reduced angiotensin II-mediated contraction, unlike nirmatrelvir and ACC519T(2).</p><p><strong>Conclusion: </strong>This study reports the discovery of a new class of benzimidazole-based sartans that significantly inhibit SARS-CoV-2, likely due to their interaction with ACE2.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199195","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":"Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.","authors":"Tingting Li, Qussay Marashly, Jitae A Kim, Na Li, Mihail G Chelu","doi":"10.1080/14728222.2024.2351501","DOIUrl":"10.1080/14728222.2024.2351501","url":null,"abstract":"<p><strong>Introduction: </strong>The cardiac conduction system (CCS) is crucial for maintaining adequate cardiac frequency at rest and modulation during exercise. Furthermore, the atrioventricular node and His-Purkinje system are essential for maintaining atrioventricular and interventricular synchrony and consequently maintaining an adequate cardiac output.</p><p><strong>Areas covered: </strong>In this review article, we examine the anatomy, physiology, and pathophysiology of the CCS. We then discuss in detail the most common genetic mutations and the molecular mechanisms of cardiac conduction disease (CCD) and provide our perspectives on future research and therapeutic opportunities in this field.</p><p><strong>Expert opinion: </strong>Significant advancement has been made in understanding the molecular mechanisms of CCD, including the recognition of the heterogeneous signaling at the subcellular levels of sinoatrial node, the involvement of inflammatory and autoimmune mechanisms, and the potential impact of epigenetic regulations on CCD. However, the current treatment of CCD manifested as bradycardia still relies primarily on cardiovascular implantable electronic devices (CIEDs). On the other hand, an I_f specific inhibitor was developed to treat inappropriate sinus tachycardia and sinus tachycardia in heart failure patients with reduced ejection fraction. More work is needed to translate current knowledge into pharmacologic or genetic interventions for the management of CCDs.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862768","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}