Expert Opinion on Therapeutic Targets最新文献_第10页

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

Veliparib (ABT-888), a PARP inhibitor potentiates the cytotoxic activity of 5-fluorouracil by inhibiting MMR pathway through deregulation of MSH6 in colorectal cancer stem cells. Veliparib（ABT-888）是一种PARP抑制剂，通过抑制结直肠癌癌症干细胞中MSH6的失调来抑制MMR途径，从而增强5-氟尿嘧啶的细胞毒性活性。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-10-30 DOI: 10.1080/14728222.2023.2266572

Subarno Paul, Subhajit Chatterjee, Saptarshi Sinha, Somya Ranjan Dash, Rajalaxmi Pradhan, Biswajit Das, Kunal Goutam, Chanakya Nath Kundu

{"title":"Veliparib (ABT-888), a PARP inhibitor potentiates the cytotoxic activity of 5-fluorouracil by inhibiting MMR pathway through deregulation of MSH6 in colorectal cancer stem cells.","authors":"Subarno Paul, Subhajit Chatterjee, Saptarshi Sinha, Somya Ranjan Dash, Rajalaxmi Pradhan, Biswajit Das, Kunal Goutam, Chanakya Nath Kundu","doi":"10.1080/14728222.2023.2266572","DOIUrl":"10.1080/14728222.2023.2266572","url":null,"abstract":"Objective: Sensitization of mismatch repair (MMR)-deficient colorectal cancer (CRC) cells by 5-Fluorouracil (5-FU) is well-documented. But not much is known about the treatment of MMR-proficient CRC cancer stem cells (CRC-CSCs). Here, we investigated whether a PARP inhibitor (ABT-888) can enhance the 5-FU-mediated apoptosis in CRC-CSCs through MMR pathway inhibition.Methods: The anti-cancer action of 5-FU+ABT-888 combination in CRC-CSCs has been studied by using in vitro, ex vivo, and in vivo preclinical model systems.Results: 5-FU caused DNA damage in CRC-CSCs, and ABT-888 enhanced the accumulation of DNA mismatches by downregulating the MMR pathway, triggering S-phase arrest, and finally apoptosis and cell death in 5-FU-pre-treated MMR-proficient-CRC-CSCs at much lower concentrations than their individual treatments. After 5-FU treatment, PARylated-PARP1 activated MMR pathway by interacting with MSH6. But, upon ABT-888 treatment in 5-FU-pre-exposed CSCs, PARylation was inhibited, as a result of which PARP1 could not interact with MSH6, and other MMR proteins were downregulated. The role of MSH6 in PARP1-mediated MMR activation, was confirmed by silencing MSH6 gene, which resulted in MMR pathway shutdown. Similar results were obtained in ex vivo and in vivo model systems.Conclusions: 5-FU+ABT-888 combination enhanced CRC-CSCs death by increasing DNA damage accumulation and simultaneously inhibiting the MMR pathway in MMR-proficient cells. But this study does not discuss whether the combination treatment will increase the sensitivity of MMR-deficient CSCs, for which further research will be performed in the future.","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":"41117869","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

Exosomes as a drug delivery tool for cancer therapy: a new era for existing drugs and oncolytic viruses. 外泌体作为癌症治疗的药物递送工具：现有药物和溶瘤病毒的新时代。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-10-13 DOI: 10.1080/14728222.2023.2259102

Yoshihiko Kakiuchi, Shinji Kuroda, Nobuhiko Kanaya, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara

{"title":"Exosomes as a drug delivery tool for cancer therapy: a new era for existing drugs and oncolytic viruses.","authors":"Yoshihiko Kakiuchi, Shinji Kuroda, Nobuhiko Kanaya, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara","doi":"10.1080/14728222.2023.2259102","DOIUrl":"10.1080/14728222.2023.2259102","url":null,"abstract":"Introduction: Exosomes are cell-derived nanovesicles involved in cell-to-cell communications. These nanovesicles are generally considered to contain important carriers of information such as DNA and RNA, and show specific tropism.Areas covered: The combination of existing therapeutic agents with exosomes enhances therapeutic effects by increasing uptake into the tumor. Induction of immunogenic cell death (ICD) may also be triggered more strongly than with the drug alone. Oncolytic viruses (OVs) are even more effective as a drug in combination with exosomes. Although OVs are more likely to cause immune activity, combination with exosomes can exert synergistic effects. OVs have potent anti-tumor effects, but many limitations, such as being limited to local administration and vulnerability to attack by antibodies. Incorporation into exosomes can overcome these limitations and may allow effects against distant tumors.Expert opinion: Novel therapies using exosomes are very attractive in terms of enhancing therapeutic efficacy and reducing side effects. This approach also contains elements overcoming disadvantages in OVs, which have not been used clinically until now, and may usher in a new era of cancer treatments.","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":"41121106","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: 1

A1BG-AS1 promotes the biological functions of osteosarcoma cells via regulating the microRNA-148a-3p/USP22 axis and stabilizing the expression of SIRT1 through deubiquitinase function. A1BG-AS1通过调节microRNA-148a-3p/USP22轴和通过去泛素酶功能稳定SIRT1的表达来促进骨肉瘤细胞的生物学功能。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-10-30 DOI: 10.1080/14728222.2023.2263908

Xiuxin Han, Mengfan Yin, Chen Gong, Chao Zhang, Genbao Zhu, Mengxue Hu, Kemeng Tan, La Jiang, Guowen Wang, Lili Li

{"title":"A1BG-AS1 promotes the biological functions of osteosarcoma cells via regulating the microRNA-148a-3p/USP22 axis and stabilizing the expression of SIRT1 through deubiquitinase function.","authors":"Xiuxin Han, Mengfan Yin, Chen Gong, Chao Zhang, Genbao Zhu, Mengxue Hu, Kemeng Tan, La Jiang, Guowen Wang, Lili Li","doi":"10.1080/14728222.2023.2263908","DOIUrl":"10.1080/14728222.2023.2263908","url":null,"abstract":"Background: The study aims to explore the role of A1BG antisense RNA 1 (A1BG-AS1), microRNA (miR)-148a-3p and ubiquitin-specific protease 22 (USP22) on osteosarcoma (OS) cell growth.Research design & methods: A1BG-AS1, miR-148a-3p, USP22, and silent information regulator 2 homolog 1 (SIRT1) levels in OS tissues and cells were determined. The effects of A1BG-AS1, miR-148a-3p, and USP22 on the biological functions of OS cells were examined by functional assays. In vivo assay was conducted to observe the effect of A1BG-AS1 on OS growth in vitro. The relationship of A1BG-AS1, miR-148a-3p, and USP22 was analyzed by bioinformatics analysis, RNA-fluorescence in situ hybridization, luciferase activity, and RNA binding protein immunoprecipitation assays. The relation between USP22 and SIRT1 was evaluated by immunoprecipitation.Results: A1BG-AS1 and USP22 were highly expressed, and miR-148a-3p was lowly expressed in OS tissues and cells. Down-regulation of A1BG-AS1 and USP22 or up-regulation of miR-148a-3p impaired the malignant behaviors of OS cells. A1BG-AS1 sponged miR-148a-3p, and miR-148a-3p targeted USP22, thereby inhibiting USP22 expression. Up-regulating USP22 reversed the A1BG-AS1 suppression-induced phenotypic inhibition of OS cells. USP22 affected the biological functions of OS cells by deubiquitinating SIRT1.Conclusion: A1BG-AS1 facilitates the biological functions of OS cells via mediating the miR-148a-3p/USP22 axis.","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":"41125074","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

Lipid-laden foam cells in the pathology of atherosclerosis: shedding light on new therapeutic targets. 脂质泡沫细胞在动脉粥样硬化病理中的作用:揭示新的治疗靶点。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-12-30 DOI: 10.1080/14728222.2023.2288272

Cristi L Galindo, Saifur Khan, Xiangyu Zhang, Yu-Sheng Yeh, Ziyang Liu, Babak Razani

{"title":"Lipid-laden foam cells in the pathology of atherosclerosis: shedding light on new therapeutic targets.","authors":"Cristi L Galindo, Saifur Khan, Xiangyu Zhang, Yu-Sheng Yeh, Ziyang Liu, Babak Razani","doi":"10.1080/14728222.2023.2288272","DOIUrl":"10.1080/14728222.2023.2288272","url":null,"abstract":"Introduction: Lipid-laden foam cells within atherosclerotic plaques are key players in all phases of lesion development including its progression, necrotic core formation, fibrous cap thinning, and eventually plaque rupture. Manipulating foam cell biology is thus an attractive therapeutic strategy at early, middle, and even late stages of atherosclerosis. Traditional therapies have focused on prevention, especially lowering plasma lipid levels. Despite these interventions, atherosclerosis remains a major cause of cardiovascular disease, responsible for the largest numbers of death worldwide.Areas covered: Foam cells within atherosclerotic plaques are comprised of macrophages, vascular smooth muscle cells, and other cell types which are exposed to high concentrations of lipoproteins accumulating within the subendothelial intimal layer. Macrophage-derived foam cells are particularly well studied and have provided important insights into lipid metabolism and atherogenesis. The contributions of foam cell-based processes are discussed with an emphasis on areas of therapeutic potential and directions for drug development.Exert opinion: As key players in atherosclerosis, foam cells are attractive targets for developing more specific, targeted therapies aimed at resolving atherosclerotic plaques. Recent advances in our understanding of lipid handling within these cells provide insights into how they might be manipulated and clinically translated to better treat atherosclerosis.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440486","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

CDK6: an attractive therapeutic target for T-ALL/LBL. CDK6: T-ALL/LBL的有吸引力的治疗靶点

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-12-07 DOI: 10.1080/14728222.2023.2285775

Wei Li, Jamie Katy Hu, Miaofen G Hu

{"title":"CDK6: an attractive therapeutic target for T-ALL/LBL.","authors":"Wei Li, Jamie Katy Hu, Miaofen G Hu","doi":"10.1080/14728222.2023.2285775","DOIUrl":"10.1080/14728222.2023.2285775","url":null,"abstract":"Introduction: Human T-cell acute lymphoblastic leukemia/T-cell lymphoblastic lymphoma (T-ALL/LBL) is a type of cancer that originates from the bone marrow and spreads quickly to other organs. Long-term survival rate with current available chemotherapy is less than 20%. Despite the potentially huge market, a truly effective and safe therapy for T-ALL/LBL is elusive. Thus, it is imperative to identify new therapeutic ways to target essential pathways in T-ALL that regulate the proliferation and survival of these cancer cells.Areas covered: The role of the Cyclin-dependent kinase 6 (CDK6) pathway in human T-ALL is of significant interest with major clinical/translational relevance. This review covers the recent advances in elucidating the essential roles of CDK6 and its closely regulated networks in proliferation, survival, and metabolism of T-ALL cells, with new insight into its mechanisms of action which hopefully could trigger the identification of new therapeutic avenues.Expert opinion: Animal models showed that inhibition of CDK6 and its related networks blocked initiation, growth, and survival of T-ALL in vivo. Numerous clinical trials of CDK4/6 inhibitors are ongoing in T-ALL. Specific CDK6 inhibitors alone or novel combination regimens may hopefully delay the progression, or even reverse the symptoms of T-ALL, leading to disease eradication and cure.","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":"136397056","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