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Annual review of pharmacology and toxicology最新文献

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LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics. LP（a）：结构、遗传学、相关心血管风险和新兴疗法。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-07-28 DOI: 10.1146/annurev-pharmtox-031023-100609
Erfan Tasdighi, Rishav Adhikari, Omar Almaadawy, Thorsten M Leucker, Michael J Blaha
{"title":"LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics.","authors":"Erfan Tasdighi, Rishav Adhikari, Omar Almaadawy, Thorsten M Leucker, Michael J Blaha","doi":"10.1146/annurev-pharmtox-031023-100609","DOIUrl":"10.1146/annurev-pharmtox-031023-100609","url":null,"abstract":"<p><p>Lipoprotein(a) [Lp(a)] is a molecule bound to apolipoprotein(a) with some similarity to low-density lipoprotein cholesterol (LDL-C), which has been found to be a risk factor for cardiovascular disease (CVD). Lp(a) appears to induce inflammation, atherogenesis, and thrombosis. Approximately 20% of the world's population has increased Lp(a) levels, determined predominantly by genetics. Current clinical practices for the management of dyslipidemia are ineffective in lowering Lp(a) levels. Evolving RNA-based therapeutics, such as the antisense oligonucleotide pelacarsen and small interfering RNA olpasiran, have shown promising results in reducing Lp(a) levels. Phase III pivotal cardiovascular outcome trials [Lp(a)HORIZON and OCEAN(a)] are ongoing to evaluate their efficacy in secondary prevention of major cardiovascular events in patients with elevated Lp(a). The future of cardiovascular residual risk reduction may transition to a personalized approach where further lowering of either LDL-C, triglycerides, or Lp(a) is selected after high-intensity statin therapy based on the individual risk profile and preferences of each patient.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"135-157"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10246320","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: 0
Orexin Receptor Antagonism: Normalizing Sleep Architecture in Old Age and Disease. 催产素受体拮抗剂：使老年和疾病患者的睡眠结构正常化
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-09-14 DOI: 10.1146/annurev-pharmtox-040323-031929
Jarrah O-Z J Kron, Ryan J Keenan, Daniel Hoyer, Laura H Jacobson
{"title":"Orexin Receptor Antagonism: Normalizing Sleep Architecture in Old Age and Disease.","authors":"Jarrah O-Z J Kron, Ryan J Keenan, Daniel Hoyer, Laura H Jacobson","doi":"10.1146/annurev-pharmtox-040323-031929","DOIUrl":"10.1146/annurev-pharmtox-040323-031929","url":null,"abstract":"<p><p>Sleep is essential for human well-being, yet the quality and quantity of sleep reduce as age advances. Older persons (>65 years old) are more at risk of disorders accompanied and/or exacerbated by poor sleep. Furthermore, evidence supports a bidirectional relationship between disrupted sleep and Alzheimer's disease (AD) or related dementias. Orexin/hypocretin neuropeptides stabilize wakefulness, and several orexin receptor antagonists (ORAs) are approved for the treatment of insomnia in adults. Dysregulation of the orexin system occurs in aging and AD, positioning ORAs as advantageous for these populations. Indeed, several clinical studies indicate that ORAs are efficacious hypnotics in older persons and dementia patients and, as in adults, are generally well tolerated. ORAs are likely to be more effective when administered early in sleep/wake dysregulation to reestablish good sleep/wake-related behaviors and reduce the accumulation of dementia-associated proteinopathic substrates. Improving sleep in aging and dementia represents a tremendous opportunity to benefit patients, caregivers, and health systems.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"359-386"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233159","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: 0
High-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions. 推进体外毒理学的高通量筛选：成就、挑战和未来方向》。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-07-28 DOI: 10.1146/annurev-pharmtox-112122-104310
Caitlin Lynch, Srilatha Sakamuru, Masato Ooka, Ruili Huang, Carleen Klumpp-Thomas, Paul Shinn, David Gerhold, Anna Rossoshek, Sam Michael, Warren Casey, Michael F Santillo, Suzanne Fitzpatrick, Russell S Thomas, Anton Simeonov, Menghang Xia
{"title":"High-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions.","authors":"Caitlin Lynch, Srilatha Sakamuru, Masato Ooka, Ruili Huang, Carleen Klumpp-Thomas, Paul Shinn, David Gerhold, Anna Rossoshek, Sam Michael, Warren Casey, Michael F Santillo, Suzanne Fitzpatrick, Russell S Thomas, Anton Simeonov, Menghang Xia","doi":"10.1146/annurev-pharmtox-112122-104310","DOIUrl":"10.1146/annurev-pharmtox-112122-104310","url":null,"abstract":"<p><p>Traditionally, chemical toxicity is determined by in vivo animal studies, which are low throughput, expensive, and sometimes fail to predict compound toxicity in humans. Due to the increasing number of chemicals in use and the high rate of drug candidate failure due to toxicity, it is imperative to develop in vitro, high-throughput screening methods to determine toxicity. The Tox21 program, a unique research consortium of federal public health agencies, was established to address and identify toxicity concerns in a high-throughput, concentration-responsive manner using a battery of in vitro assays. In this article, we review the advancements in high-throughput robotic screening methodology and informatics processes to enable the generation of toxicological data, and their impact on the field; further, we discuss the future of assessing environmental toxicity utilizing efficient and scalable methods that better represent the corresponding biological and toxicodynamic processes in humans.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"191-209"},"PeriodicalIF":11.2,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10822017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10246325","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
Pharmacogenomics Beyond Single Common Genetic Variants: The Way Forward. 药物基因组学超越单一常见基因变异：前进之路。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-07-28 DOI: 10.1146/annurev-pharmtox-051921-091209
Volker M Lauschke, Yitian Zhou, Magnus Ingelman-Sundberg
{"title":"Pharmacogenomics Beyond Single Common Genetic Variants: The Way Forward.","authors":"Volker M Lauschke, Yitian Zhou, Magnus Ingelman-Sundberg","doi":"10.1146/annurev-pharmtox-051921-091209","DOIUrl":"10.1146/annurev-pharmtox-051921-091209","url":null,"abstract":"<p><p>Interindividual variability in genes encoding drug-metabolizing enzymes, transporters, receptors, and human leukocyte antigens has a major impact on a patient's response to drugs with regard to efficacy and safety. Enabled by both technological and conceptual advances, the field of pharmacogenomics is developing rapidly. Major progress in omics profiling methods has enabled novel genotypic and phenotypic characterization of patients and biobanks. These developments are paralleled by advances in machine learning, which have allowed us to parse the immense wealth of data and establish novel genetic markers and polygenic models for drug selection and dosing. Pharmacogenomics has recently become more widespread in clinical practice to personalize treatment and to develop new drugs tailored to specific patient populations. In this review, we provide an overview of the latest developments in the field and discuss the way forward, including how to address the missing heritability, develop novel polygenic models, and further improve the clinical implementation of pharmacogenomics.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"33-51"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10264298","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: 0
Antiepileptic Drugs as Potential Dementia Prophylactics Following Traumatic Brain Injury. 抗癫痫药物作为创伤性脑损伤后潜在的痴呆预防药物。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-10-03 DOI: 10.1146/annurev-pharmtox-051921-013930
Laszlo F Locskai, Hadeel Alyenbaawi, W Ted Allison
{"title":"Antiepileptic Drugs as Potential Dementia Prophylactics Following Traumatic Brain Injury.","authors":"Laszlo F Locskai, Hadeel Alyenbaawi, W Ted Allison","doi":"10.1146/annurev-pharmtox-051921-013930","DOIUrl":"10.1146/annurev-pharmtox-051921-013930","url":null,"abstract":"<p><p>Seizures and other forms of neurovolatility are emerging as druggable prodromal mechanisms that link traumatic brain injury (TBI) to the progression of later dementias. TBI neurotrauma has both acute and long-term impacts on health, and TBI is a leading risk factor for dementias, including chronic traumatic encephalopathy and Alzheimer's disease. Treatment of TBI already considers acute management of posttraumatic seizures and epilepsy, and impressive efforts have optimized regimens of antiepileptic drugs (AEDs) toward that goal. Here we consider that expanding these management strategies could determine which AED regimens best prevent dementia progression in TBI patients. Challenges with this prophylactic strategy include the potential consequences of prolonged AED treatment and that a large subset of patients are refractory to available AEDs. Addressing these challenges is warranted because the management of seizure activity following TBI offers a rare opportunity to prevent the onset or progression of devastating dementias.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"577-598"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112201","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: 0
Introduction to the Theme "Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment". 药理学个体性：个性化和精准药物治疗的新见解和新策略 "主题介绍：个性化和精确药物治疗的新见解和新策略"。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-10-10 DOI: 10.1146/annurev-pharmtox-090123-010552
Urs A Meyer, Susan G Amara, Terrence F Blaschke, Paul A Insel
{"title":"Introduction to the Theme \"Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment\".","authors":"Urs A Meyer, Susan G Amara, Terrence F Blaschke, Paul A Insel","doi":"10.1146/annurev-pharmtox-090123-010552","DOIUrl":"10.1146/annurev-pharmtox-090123-010552","url":null,"abstract":"<p><p>The reviews in Volume 64 of the <i>Annual Review of Pharmacology and Toxicology</i> cover diverse topics. A common theme in many of the reviews is the interindividual variability in the clinical response to drugs. Highlighted areas include emerging developments in pharmacogenomics that can predict the personal risk for drug inefficacy and/or adverse drug reactions. Other reviews focus on the use of circulating biomarkers to define drug metabolism phenotypes and the effect of circadian regulation on drug response. Another emerging technology, digital twins that model individual patients, is used to generate computational simulations of drug effects and identify optimal personalized treatments. Another variable that may affect clinical outcomes, the nocebo response (an adverse reaction to a placebo), complicates clinical trials. These reviews further document that pharmacological individuality is an essential component of the concepts of personalized medicine and precision medicine and will likely have an important impact on patient care.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"64 ","pages":"27-31"},"PeriodicalIF":11.2,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519495","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: 0
Addressing Ancestry and Sex Bias in Pharmacogenomics. 解决药物基因组学中的血统和性别偏见。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-07-14 DOI: 10.1146/annurev-pharmtox-030823-111731
Manuel Corpas, Moneeza K Siddiqui, Opeyemi Soremekun, Rohini Mathur, Dipender Gill, Segun Fatumo
{"title":"Addressing Ancestry and Sex Bias in Pharmacogenomics.","authors":"Manuel Corpas, Moneeza K Siddiqui, Opeyemi Soremekun, Rohini Mathur, Dipender Gill, Segun Fatumo","doi":"10.1146/annurev-pharmtox-030823-111731","DOIUrl":"10.1146/annurev-pharmtox-030823-111731","url":null,"abstract":"<p><p>The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic variants and drug efficacy or toxicity, we are able to optimize pharmacological therapy according to an individual's genotype. Pharmacogenomics research has historically suffered from bias and underrepresentation of people from certain ancestry groups and of the female sex. These biases can arise from factors such as drugs and indications studied, selection of study participants, and methods used to collect and analyze data. To examine the representation of biogeographical populations in pharmacogenomic data sets, we describe individuals involved in gene-drug response studies from PharmGKB, a leading repository of drug-gene annotations, and showcase<i>CYP2D6</i>, a gene that metabolizes approximately 25% of all prescribed drugs. We also show how the historical underrepresentation of females in clinical trials has led to significantly more adverse drug reactions in females than in males.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"53-64"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9779570","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: 0
Targeting Efferocytosis in Inflammaging. 在炎症过程中以吞噬细胞为目标
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-08-16 DOI: 10.1146/annurev-pharmtox-032723-110507
Ivan K H Poon, Kodi S Ravichandran
{"title":"Targeting Efferocytosis in Inflammaging.","authors":"Ivan K H Poon, Kodi S Ravichandran","doi":"10.1146/annurev-pharmtox-032723-110507","DOIUrl":"10.1146/annurev-pharmtox-032723-110507","url":null,"abstract":"<p><p>Rapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance of tissue homeostasis, the resolution of inflammation, and tissue repair. However, impaired efferocytosis can result in the accumulation of apoptotic cells, subsequently triggering sterile inflammation through the release of endogenous factors such as DNA and nuclear proteins from membrane permeabilized dying cells. Here, we review the molecular basis of the three key phases of efferocytosis, that is, the detection, uptake, and degradation of apoptotic materials by phagocytes. We also discuss how defects in efferocytosis due to the alteration of phagocytes and dying cells can contribute to the low-grade chronic inflammation that occurs during aging, described as inflammaging. Lastly, we explore opportunities in targeting and harnessing the efferocytic machinery to limit aging-associated inflammatory diseases.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"339-357"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10013250","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: 0
Gene-Environment Interactions: My Unique Journey. 基因与环境的相互作用：我独特的旅程。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-10-03 DOI: 10.1146/annurev-pharmtox-022323-082311
Daniel W Nebert
{"title":"Gene-Environment Interactions: My Unique Journey.","authors":"Daniel W Nebert","doi":"10.1146/annurev-pharmtox-022323-082311","DOIUrl":"10.1146/annurev-pharmtox-022323-082311","url":null,"abstract":"<p><p>I am deeply honored to be invited to write this scientific autobiography. As a physician-scientist, pediatrician, molecular biologist, and geneticist, I have authored/coauthored more than 600 publications in the fields of clinical medicine, biochemistry, biophysics, pharmacology, drug metabolism, toxicology, molecular biology, cancer, standardized gene nomenclature, developmental toxicology and teratogenesis, mouse genetics, human genetics, and evolutionary genomics. Looking back, I think my career can be divided into four distinct research areas, which I summarize mostly chronologically in this article: (<i>a</i>) discovery and characterization of the AHR/CYP1 axis, (<i>b</i>) pharmacogenomics and genetic prediction of response to drugs and other environmental toxicants, (<i>c</i>) standardized drug-metabolizing gene nomenclature based on evolutionary divergence, and (<i>d</i>) discovery and characterization of the <i>SLC39A8</i> gene encoding the ZIP8 metal cation influx transporter. Collectively, all four topics embrace gene-environment interactions, hence the title of my autobiography.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"1-26"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41091887","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: 0
G Protein-Coupled Receptor Signaling: New Insights Define Cellular Nanodomains. G 蛋白偶联受体信号：定义细胞纳米域的新见解。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-09-08 DOI: 10.1146/annurev-pharmtox-040623-115054
Martin J Lohse, Andreas Bock, Manuela Zaccolo
{"title":"G Protein-Coupled Receptor Signaling: New Insights Define Cellular Nanodomains.","authors":"Martin J Lohse, Andreas Bock, Manuela Zaccolo","doi":"10.1146/annurev-pharmtox-040623-115054","DOIUrl":"10.1146/annurev-pharmtox-040623-115054","url":null,"abstract":"<p><p>G protein-coupled receptors are the largest and pharmacologically most important receptor family and are involved in the regulation of most cell functions. Most of them reside exclusively at the cell surface, from where they signal via heterotrimeric G proteins to control the production of second messengers such as cAMP and IP<sub>3</sub> as well as the activity of several ion channels. However, they may also internalize upon agonist stimulation or constitutively reside in various intracellular locations. Recent evidence indicates that their function differs depending on their precise cellular localization. This is because the signals they produce, notably cAMP and Ca<sup>2+</sup>, are mostly bound to cell proteins that significantly reduce their mobility, allowing the generation of steep concentration gradients. As a result, signals generated by the receptors remain confined to nanometer-sized domains. We propose that such nanometer-sized domains represent the basic signaling units in a cell and a new type of target for drug development.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"387-415"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10187019","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: 0
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