Annual review of pharmacology and toxicology最新文献_第10页

CaMKII as a Therapeutic Target in Cardiovascular Disease. 作为心血管疾病治疗靶点的 CaMKII。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 Epub Date: 2022-08-16 DOI: 10.1146/annurev-pharmtox-051421-111814

Oscar E Reyes Gaido, Lubika J Nkashama, Kate L Schole, Qinchuan Wang, Priya Umapathi, Olurotimi O Mesubi, Klitos Konstantinidis, Elizabeth D Luczak, Mark E Anderson

{"title":"CaMKII as a Therapeutic Target in Cardiovascular Disease.","authors":"Oscar E Reyes Gaido, Lubika J Nkashama, Kate L Schole, Qinchuan Wang, Priya Umapathi, Olurotimi O Mesubi, Klitos Konstantinidis, Elizabeth D Luczak, Mark E Anderson","doi":"10.1146/annurev-pharmtox-051421-111814","DOIUrl":"10.1146/annurev-pharmtox-051421-111814","url":null,"abstract":"CaMKII (the multifunctional Ca2+ and calmodulin-dependent protein kinase II) is a highly validated signal for promoting a variety of common diseases, particularly in the cardiovascular system. Despite substantial amounts of convincing preclinical data, CaMKII inhibitors have yet to emerge in clinical practice. Therapeutic inhibition is challenged by the diversity of CaMKII isoforms and splice variants and by physiological CaMKII activity that contributes to learning and memory. Thus, uncoupling the harmful and beneficial aspects of CaMKII will be paramount to developing effective therapies. In the last decade, several targeting strategies have emerged, including small molecules, peptides, and nucleotides, which hold promise in discriminating pathological from physiological CaMKII activity. Here we review the cellular and molecular biology of CaMKII, discuss its role in physiological and pathological signaling, and consider new findings and approaches for developing CaMKII therapeutics.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"63 ","pages":"249-272"},"PeriodicalIF":12.5,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9120748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Neuropathic Pain: Mechanisms, Sex Differences, and Potential Therapies for a Global Problem. 神经性疼痛：机理、性别差异和解决全球性问题的潜在疗法。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI: 10.1146/annurev-pharmtox-051421-112259

Shahrzad Ghazisaeidi, Milind M Muley, Michael W Salter

{"title":"Neuropathic Pain: Mechanisms, Sex Differences, and Potential Therapies for a Global Problem.","authors":"Shahrzad Ghazisaeidi, Milind M Muley, Michael W Salter","doi":"10.1146/annurev-pharmtox-051421-112259","DOIUrl":"10.1146/annurev-pharmtox-051421-112259","url":null,"abstract":"The study of chronic pain continues to generate ever-increasing numbers of publications, but safe and efficacious treatments for chronic pain remain elusive. Recognition of sex-specific mechanisms underlying chronic pain has resulted in a surge of studies that include both sexes. A predominant focus has been on identifying sex differences, yet many newly identified cellular mechanisms and alterations in gene expression are conserved between the sexes. Here we review sex differences and similarities in cellular and molecular signals that drive the generation and resolution of neuropathic pain. The mix of differences and similarities reflects degeneracy in peripheral and central signaling processes by which neurons, immune cells, and glia codependently drive pain hypersensitivity. Recent findings identifying critical signaling nodes foreshadow the development of rationally designed, broadly applicable analgesic strategies. However, the paucity of effective, safe pain treatments compels targeted therapies as well to increase therapeutic options that help reduce the global burden of suffering.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"63 ","pages":"565-583"},"PeriodicalIF":12.5,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9126126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 20

Noncanonical Metabotropic Glutamate Receptor 5 Signaling in Alzheimer's Disease. 非典型代谢性谷氨酸受体5信号在阿尔茨海默病中的作用。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2022-01-06 Epub Date: 2021-09-13 DOI: 10.1146/annurev-pharmtox-021821-091747

Khaled S Abd-Elrahman, Stephen S G Ferguson

{"title":"Noncanonical Metabotropic Glutamate Receptor 5 Signaling in Alzheimer's Disease.","authors":"Khaled S Abd-Elrahman, Stephen S G Ferguson","doi":"10.1146/annurev-pharmtox-021821-091747","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-021821-091747","url":null,"abstract":"Metabotropic glutamate receptor 5 (mGluR5) is ubiquitously expressed in brain regions responsible for memory and learning. It plays a key role in modulating rapid changes in synaptic transmission and plasticity. mGluR5 supports long-term changes in synaptic strength by regulating the transcription and translation of essential synaptic proteins. β-Amyloid 42 (Aβ42) oligomers interact with a mGluR5/cellular prion protein (PrPC) complex to disrupt physiological mGluR5 signal transduction. Aberrant mGluR5 signaling and associated synaptic failure are considered an emerging pathophysiological mechanism of Alzheimer's disease (AD). Therefore, mGluR5 represents an attractive therapeutic target for AD, and recent studies continue to validate the efficacy of various mGluR5 allosteric modulators in improving memory deficits and mitigating disease pathology. However, sex-specific differences in the pharmacology of mGluR5 and activation of noncanonical signaling downstream of the receptor suggest that its utility as a therapeutic target in female AD patients needs to be reconsidered.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"235-254"},"PeriodicalIF":12.5,"publicationDate":"2022-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39414454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 19

Repurposing Colchicine for Heart Disease. 秋水仙碱对心脏病的再利用

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2022-01-06 Epub Date: 2021-09-30 DOI: 10.1146/annurev-pharmtox-052120-020445

Nadia Bouabdallaoui, Jean-Claude Tardif

引用次数: 3

KCNQ Potassium Channels as Targets of Botanical Folk Medicines. 作为民间植物药靶点的 KCNQ 钾通道

IF 11.2 1区医学

Annual review of pharmacology and toxicology Pub Date : 2022-01-06 Epub Date: 2021-09-13 DOI: 10.1146/annurev-pharmtox-052120-104249

Kaitlyn E Redford, Geoffrey W Abbott

{"title":"KCNQ Potassium Channels as Targets of Botanical Folk Medicines.","authors":"Kaitlyn E Redford, Geoffrey W Abbott","doi":"10.1146/annurev-pharmtox-052120-104249","DOIUrl":"10.1146/annurev-pharmtox-052120-104249","url":null,"abstract":"Since prehistory, human species have depended on plants for both food and medicine. Even in countries with ready access to modern medicines, alternative treatments are still highly regarded and commonly used. Unlike modern pharmaceuticals, many botanical medicines are in widespread use despite a lack of safety and efficacy data derived from controlled clinical trials and often unclear mechanisms of action. Contributing to this are the complex and undefined composition and likely multifactorial mechanisms of action and multiple targets of many botanical medicines. Here, we review the newfound importance of the ubiquitous KCNQ subfamily of voltage-gated potassium channels as targets for botanical medicines, including basil, capers, cilantro, lavender, fennel, chamomile, ginger, and Camellia, Sophora, and Mallotus species. We discuss the implications for the traditional use of these plants for disorders such as seizures, hypertension, and diabetes and the molecular mechanisms of plant secondary metabolite effects on KCNQ channels.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"62 ","pages":"447-464"},"PeriodicalIF":11.2,"publicationDate":"2022-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9809153/pdf/nihms-1857008.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10491528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Central Nervous System Control of Glucose Homeostasis: A Therapeutic Target for Type 2 Diabetes? 中枢神经系统对葡萄糖稳态的控制：2 型糖尿病的治疗目标？

IF 11.2 1区医学

Annual review of pharmacology and toxicology Pub Date : 2022-01-06 DOI: 10.1146/annurev-pharmtox-052220-010446

Zaman Mirzadeh, Chelsea L Faber, Michael W Schwartz

引用次数: 0

Thioredoxin Reductase Inhibition for Cancer Therapy. 抑制硫氧还蛋白还原酶治疗癌症。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2022-01-06 Epub Date: 2021-08-24 DOI: 10.1146/annurev-pharmtox-052220-102509

Radosveta Gencheva, Elias S J Arnér

引用次数: 54

Measuring Pharmacogene Variant Function at Scale Using Multiplexed Assays. 使用多重测定法大规模测量药物基因变异功能。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2022-01-06 Epub Date: 2021-09-13 DOI: 10.1146/annurev-pharmtox-032221-085807

Renee C Geck, Gabriel Boyle, Clara J Amorosi, Douglas M Fowler, Maitreya J Dunham

引用次数: 6

Emerging Therapeutics, Technologies, and Drug Development Strategies to Address Patient Nonadherence and Improve Tuberculosis Treatment. 新兴疗法、技术和药物开发策略解决患者不依从和改善结核病治疗。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2022-01-06 Epub Date: 2021-09-30 DOI: 10.1146/annurev-pharmtox-041921-074800

Maria Garcia-Cremades, Belen P Solans, Natasha Strydom, Bernard Vrijens, Goonaseelan Colin Pillai, Craig Shaffer, Bruce Thomas, Rada M Savic

{"title":"Emerging Therapeutics, Technologies, and Drug Development Strategies to Address Patient Nonadherence and Improve Tuberculosis Treatment.","authors":"Maria Garcia-Cremades, Belen P Solans, Natasha Strydom, Bernard Vrijens, Goonaseelan Colin Pillai, Craig Shaffer, Bruce Thomas, Rada M Savic","doi":"10.1146/annurev-pharmtox-041921-074800","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-041921-074800","url":null,"abstract":"Imperfect medication adherence remains the biggest predictor of treatment failure for patients with tuberculosis. Missed doses during treatment lead to relapse, tuberculosis resistance, and further spread of disease. Understanding individual patient phenotypes, population pharmacokinetics, resistance development, drug distribution to tuberculosis lesions, and pharmacodynamics at the site of infection is necessary to fully measure the impact of adherence on patient outcomes. To decrease the impact of expected variabilityin drug intake on tuberculosis outcomes, an improvement in patient adherence and new forgiving regimens that protect against missed doses are needed. In this review, we summarize emerging technologies to improve medication adherence in clinical practice and provide suggestions on how digital adherence technologies can be incorporated in clinical trials and practice and the drug development pipeline that will lead to more forgiving regimens and benefit patients suffering from tuberculosis.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"197-210"},"PeriodicalIF":12.5,"publicationDate":"2022-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39473152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 8

Targeting NRF2 and Its Downstream Processes: Opportunities and Challenges. 靶向NRF2及其下游过程:机遇与挑战。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2022-01-06 Epub Date: 2021-09-09 DOI: 10.1146/annurev-pharmtox-052220-104025

Laura Torrente, Gina M DeNicola

引用次数: 49