Expert Opinion on Therapeutic Targets最新文献_第8页

Advances in cerebellar disorders: pre-clinical models, therapeutic targets, and challenges. 小脑疾病的进展：临床前模型、治疗靶点和挑战。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-10-30 DOI: 10.1080/14728222.2023.2263911

Mario Manto, Jan Cendelin, Michael Strupp, Hiroshi Mitoma

{"title":"Advances in cerebellar disorders: pre-clinical models, therapeutic targets, and challenges.","authors":"Mario Manto, Jan Cendelin, Michael Strupp, Hiroshi Mitoma","doi":"10.1080/14728222.2023.2263911","DOIUrl":"10.1080/14728222.2023.2263911","url":null,"abstract":"Introduction: Cerebellar ataxias (CAs) represent neurological disorders with multiple etiologies and a high phenotypic variability. Despite progress in the understanding of pathogenesis, few therapies are available so far. Closing the loop between preclinical studies and therapeutic trials is important, given the impact of CAs upon patients' health and the roles of the cerebellum in multiple domains. Because of a rapid advance in research on CAs, it is necessary to summarize the main findings and discuss future directions.Areas covered: We focus our discussion on preclinical models, cerebellar reserve, the therapeutic management of CAs, and suitable surrogate markers. We searched Web of Science and PubMed using keywords relevant to cerebellar diseases, therapy, and preclinical models.Expert opinion: There are many symptomatic and/or disease-modifying therapeutic approaches under investigation. For therapy development, preclinical studies, standardization of disease evaluation, safety assessment, and demonstration of clinical improvements are essential. Stage of the disease and the level of the cerebellar reserve determine the goals of the therapy. Deficits in multiple categories and heterogeneity of CAs may require disease-, stage-, and symptom-specific therapies. More research is needed to clarify how therapies targeting the cerebellum influence both basal ganglia and the cerebral cortex, poorly explored domains in CAs.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41096849","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}

引用次数: 0

Pleural mesothelioma: a snapshot of emerging drug targets and opportunities for non-surgical therapeutic advancement. 胸膜间皮瘤：新出现的药物靶点和非手术治疗进展机会的快照。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-12-07 DOI: 10.1080/14728222.2023.2277224

Jean-Baptiste Assié, Didier Jean

{"title":"Pleural mesothelioma: a snapshot of emerging drug targets and opportunities for non-surgical therapeutic advancement.","authors":"Jean-Baptiste Assié, Didier Jean","doi":"10.1080/14728222.2023.2277224","DOIUrl":"10.1080/14728222.2023.2277224","url":null,"abstract":"Introduction: Pleural mesothelioma is a rare and aggressive cancer originating in the pleura, with a devastating prognosis and limited treatment options. There have been significant advancements in the management of this disease in recent years. Since 2021, nivolumab and ipilimumab immune checkpoint inhibitors have become the new standard of care for first-line treatment of pleural mesothelioma.Areas covered: While a combination of chemotherapy and immune checkpoint inhibitors appears to be the next step, targeted therapies are emerging thanks to our understanding of the oncogenesis of pleural mesothelioma. Moreover, several new strategies are currently being investigated, including viral therapy, antibody-drug conjugates, and even cell therapies with CAR-T cells or dendritic cells. In this review, we will explore the various future opportunities that could potentially transform patients' lives in light of the clinical trials that have been conducted.Expert opinion: Future clinical studies aim to rebiopsy patients after disease progression to identify new molecular alterations and to be associated with ancillary studies, guiding subsequent therapy decisions. Predicting and investigating treatment resistance mechanisms will lead to innovative approaches and improved treatment outcomes.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411173","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}

引用次数: 0

miR-26a-5p restoration via EZH2 silencing blocks the IL-6/STAT3 axis to repress the growth of prostate cancer. 通过 EZH2 沉默恢复 miR-26a-5p 可阻断 IL-6/STAT3 轴，从而抑制前列腺癌的生长。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-12-30 DOI: 10.1080/14728222.2023.2293750

Wenqiang Zhang, Qiwei Nie, Xuling Zhang, Long Huang, Guofu Pang, Jing Chu, Xiaoxu Yuan

{"title":"miR-26a-5p restoration via EZH2 silencing blocks the IL-6/STAT3 axis to repress the growth of prostate cancer.","authors":"Wenqiang Zhang, Qiwei Nie, Xuling Zhang, Long Huang, Guofu Pang, Jing Chu, Xiaoxu Yuan","doi":"10.1080/14728222.2023.2293750","DOIUrl":"10.1080/14728222.2023.2293750","url":null,"abstract":"Background: Interleukin-6 (IL-6) is involved in the activation of several oncogenic pathways in prostate cancer. However, its upstream trans-signaling pathway remains largely unknown. This work proposes a mechanistic explanation of IL-6's upstream effectors in prostate carcinogenesis.Research design & methods: Samples were harvested to validate the expression of EZH2, miR-26a-5p, and IL-6. Moreover, the protein and its phosphorylation of STAT3 (signal transducer and transcription activator 3) were assessed in prostate cancer cells. We explored the effects of these effectors on malignant phenotypes in vitro and tumor growth in vivo using functional assays. Bioinformatics analysis, dual-luciferase reporter gene assays, and chromatin immunoprecipitation (ChIP) assays were used to determine their binding relationships.Results: Overexpression of EZH2 and IL-6, and under expression of miR-26a-5p was observed in prostate cancer. Silencing IL-6 repressed STAT3 to suppress the malignant phenotypes of prostate cancer cells. Mechanistically, EZH2 inhibited miR-26a-5p expression by promoting H3K27 histone methylation, and miR-26a-5p restricted the malignant phenotypes of prostate cancer by targeting IL-6. Ectopic EZH2 expression reduced xenograft growth by inhibiting miR-26a-5p and activating the IL-6/STAT3 axis.Conclusion: EZH2 May potentially be involved in regulating its expression by recruiting H3K27me3 to the miR-26a-5p promoter region, which could further impact the IL6/STAT3 pathway.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058265","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}

引用次数: 0

Targeting cyclin-dependent kinases in rheumatoid arthritis and psoriasis - a review of current evidence. 靶向周期蛋白依赖性激酶治疗类风湿性关节炎和牛皮癣-当前证据综述

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-12-07 DOI: 10.1080/14728222.2023.2285784

Marzena Staniszewska, Kajetan Kiełbowski, Klaudia Rusińska, Estera Bakinowska, Ewa Gromowska, Andrzej Pawlik

{"title":"Targeting cyclin-dependent kinases in rheumatoid arthritis and psoriasis - a review of current evidence.","authors":"Marzena Staniszewska, Kajetan Kiełbowski, Klaudia Rusińska, Estera Bakinowska, Ewa Gromowska, Andrzej Pawlik","doi":"10.1080/14728222.2023.2285784","DOIUrl":"10.1080/14728222.2023.2285784","url":null,"abstract":"Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with synovial proliferation and bone erosion, which leads to the structural and functional impairment of the joints. Immune cells, together with synoviocytes, induce a pro-inflammatory environment and novel treatment agents target inflammatory cytokines. Psoriasis is a chronic immune-mediated skin disease, and several cytokines are considered as typical mediators in the progression of the disease, including IL-23, IL-22, and IL-17, among others.Area covered: In this review, we try to evaluate whether cyclin-dependent kinases (CDK), enzymes that regulate cell cycle and transcription of various genes, could become novel therapeutic targets in RA and psoriasis. We present the main results of in vitro and in vivo studies, as well as scarce clinical reports.Expert opinion: CDK inhibitors seem promising for treating RA and psoriasis because of their multidirectional effects. CDK inhibitors may affect not only the process of osteoclastogenesis, thereby reducing joint destruction in RA, but also the process of apoptosis of neutrophils and macrophages responsible for the development of inflammation in both RA and psoriasis. However, assessing the efficacy of these drugs in clinical practice requires multi-center, long-term clinical trials evaluating the effectiveness and safety of CDK-blocking therapy in RA and psoriasis.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138046676","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}

引用次数: 0

Is chymase 1 a therapeutic target in cardiovascular disease? 糜蛋白酶1是心血管疾病的治疗靶点吗？

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-08-21 DOI: 10.1080/14728222.2023.2247561

Carlos M Ferrario, Sarfaraz Ahmad, Robert Speth, Louis J Dell'Italia

{"title":"Is chymase 1 a therapeutic target in cardiovascular disease?","authors":"Carlos M Ferrario, Sarfaraz Ahmad, Robert Speth, Louis J Dell'Italia","doi":"10.1080/14728222.2023.2247561","DOIUrl":"10.1080/14728222.2023.2247561","url":null,"abstract":"Introduction: Non-angiotensin converting enzyme mechanisms of angiotensin II production remain underappreciated in part due to the success of current therapies to ameliorate the impact of primary hypertension and atherosclerotic diseases of the heart and the blood vessels. This review scrutinize the current literature to highlight chymase role as a critical participant in the pathogenesis of cardiovascular disease and heart failure.Areas covered: We review the contemporaneous understanding of circulating and tissue biotransformation mechanisms of the angiotensins focusing on the role of chymase as an alternate tissue generating pathway for angiotensin II pathological mechanisms of action.Expert opinion: While robust literature documents the singularity of chymase as an angiotensin II-forming enzyme, particularly when angiotensin converting enzyme is inhibited, this knowledge has not been fully recognized to clinical medicine. This review discusses the limitations of clinical trials' that explored the benefits of chymase inhibition in accounting for the failure to duplicate in humans what has been demonstrated in experimental animals.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030495","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}

引用次数: 0

The role of the ATP-Binding Cassette A1 (ABCA1) in neurological disorders: a mechanistic review. ATP结合盒A1（ABCA1）在神经系统疾病中的作用：机制综述。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-07-17 DOI: 10.1080/14728222.2023.2235718

Tahere Paseban, Mohaddeseh Sadat Alavi, Leila Etemad, Ali Roohbakhsh

{"title":"The role of the ATP-Binding Cassette A1 (ABCA1) in neurological disorders: a mechanistic review.","authors":"Tahere Paseban, Mohaddeseh Sadat Alavi, Leila Etemad, Ali Roohbakhsh","doi":"10.1080/14728222.2023.2235718","DOIUrl":"10.1080/14728222.2023.2235718","url":null,"abstract":"Introduction: Cholesterol homeostasis is critical for normal brain function. It is tightly controlled by various biological elements. ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that effluxes cholesterol from cells, particularly astrocytes, into the extracellular space. The recent studies pertaining to ABCA1's role in CNS disorders were included in this study.Areas covered: In this comprehensive literature review, preclinical and human studies showed that ABCA1 has a significant role in the following diseases or disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, neuropathy, anxiety, depression, psychosis, epilepsy, stroke, and brain ischemia and trauma.Expert opinion: ABCA1 via modulating normal and aberrant brain functions such as apoptosis, phagocytosis, BBB leakage, neuroinflammation, amyloid β efflux, myelination, synaptogenesis, neurite outgrowth, and neurotransmission promotes beneficial effects in aforementioned diseases. ABCA1 is a key molecule in the CNS. By boosting its expression or function, some CNS disorders may be resolved. In preclinical studies, liver X receptor agonists have shown promise in treating CNS disorders via ABCA1 and apoE enhancement.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10020812","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}

引用次数: 0

ORF6, a repressor of the MHC class I pathway: new molecular target for SARS-CoV-2 drug discovery? ORF6，MHC I类通路的阻遏物：严重急性呼吸系统综合征冠状病毒2型药物发现的新分子靶点？

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-08-30 DOI: 10.1080/14728222.2023.2248377

Baohui Zhu, Ryota Ouda, Paul de Figueiredo, Koichi S Kobayashi

引用次数: 0

Seizure-suppressor genes: can they help spearhead the discovery of novel therapeutic targets for epilepsy? 癫痫抑制基因：它们能帮助率先发现新的癫痫治疗靶点吗？

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-08-22 DOI: 10.1080/14728222.2023.2248375

Gleice Kelli Silva-Cardoso, Prosper N'Gouemo

{"title":"Seizure-suppressor genes: can they help spearhead the discovery of novel therapeutic targets for epilepsy?","authors":"Gleice Kelli Silva-Cardoso, Prosper N'Gouemo","doi":"10.1080/14728222.2023.2248375","DOIUrl":"10.1080/14728222.2023.2248375","url":null,"abstract":"Introduction: Epilepsies are disorders of neuronal excitability characterized by spontaneously recurrent focal and generalized seizures, some of which result from genetic mutations. Despite the availability of antiseizure medications, pharmaco-resistant epilepsy is seen in about 23% of epileptic patients worldwide. Therefore, there is an urgent need to develop novel therapeutic strategies for epilepsies. Several epilepsy-associated genes have been found in humans. Seizure susceptibility can also be induced in Drosophila mutants, some showing features resembling human epilepsies. Interestingly, several second-site mutation gene products have been found to suppress seizure susceptibility in the seizure genetic model Drosophila. Thus, these so-called 'seizure-suppressor' gene variants may lead to developing a novel class of antiseizure medications.Area covered: This review evaluates the potential therapeutic of seizure-suppressor gene variants.Expert opinion: Studies on epilepsy-associated genes have allowed analyses of mutations linked to human epilepsy by reproducing these mutations in Drosophila using reverse genetics to generate potential antiseizure therapeutics. As a result, about fifteen seizure-suppressor gene mutants have been identified. Furthermore, some of these epilepsy gene mutations affect ligand-and voltage-gated ion channels. Therefore, a better understanding of the antiseizure activity of seizure-suppressor genes is essential in advancing gene therapy and precision medicine for epilepsy.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039471","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}

引用次数: 0

Human prion disease: molecular pathogenesis, and possible therapeutic targets and strategies. 人类朊病毒病：分子发病机制以及可能的治疗目标和策略。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-06-19 DOI: 10.1080/14728222.2023.2199923

Simone Baiardi, Angela Mammana, Sabina Capellari, Piero Parchi

{"title":"Human prion disease: molecular pathogenesis, and possible therapeutic targets and strategies.","authors":"Simone Baiardi, Angela Mammana, Sabina Capellari, Piero Parchi","doi":"10.1080/14728222.2023.2199923","DOIUrl":"10.1080/14728222.2023.2199923","url":null,"abstract":"Introduction: Human prion diseases are heterogeneous, and often rapidly progressive, transmissible neurodegenerative disorders associated with misfolded prion protein (PrP) aggregation and self-propagation. Despite their rarity, prion diseases comprise a broad spectrum of phenotypic variants determined at the molecular level by different conformers of misfolded PrP and host genotype variability. Moreover, they uniquely occur in idiopathic, genetically determined, and acquired forms with distinct etiologies.Area covered: This review provides an up-to-date overview of potential therapeutic targets in prion diseases and the main results obtained in cell and animal models and human trials. The open issues and challenges associated with developing effective therapies and informative clinical trials are also discussed.Expert opinion: Currently tested therapeutic strategies target the cellular PrP to prevent the formation of misfolded PrP or to favor its elimination. Among them, passive immunization and gene therapy with antisense oligonucleotides against prion protein mRNA are the most promising. However, the disease's rarity, heterogeneity, and rapid progression profoundly frustrate the successful undertaking of well-powered therapeutic trials and patient identification in the asymptomatic or early stage before the development of significant brain damage. Thus, the most promising therapeutic goal to date is preventing or delaying phenoconversion in carriers of pathogenic mutations by lowering prion protein expression.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10019474","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}

引用次数: 0

The ATP-sensitive potassium channel: a therapeutic target for neurodegeneration? ATP敏感性钾通道：神经退行性变的治疗靶点？

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-08-01 DOI: 10.1080/14728222.2023.2240023

Xue Xiao, Mingxia Bi, Xixun Du, Hong Jiang

引用次数: 0