Pharmacology & Therapeutics最新文献_第10页

Nutraceuticals target androgen receptor-splice variants (AR-SV) to manage castration resistant prostate cancer (CRPC) 营养保健品以雄激素受体拼接变体（AR-SV）为靶点，用于治疗对阉割有抵抗力的前列腺癌（CRPC）。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-02 DOI: 10.1016/j.pharmthera.2024.108743

Ashish Tyagi , Balaji Chandrasekaran , Vaibhav Shukla , Neha Tyagi , Arun K. Sharma , Chendil Damodaran

{"title":"Nutraceuticals target androgen receptor-splice variants (AR-SV) to manage castration resistant prostate cancer (CRPC)","authors":"Ashish Tyagi , Balaji Chandrasekaran , Vaibhav Shukla , Neha Tyagi , Arun K. Sharma , Chendil Damodaran","doi":"10.1016/j.pharmthera.2024.108743","DOIUrl":"10.1016/j.pharmthera.2024.108743","url":null,"abstract":"<div><div>Every year, prostate cancer is diagnosed in millions of men. The androgen receptor's (AR) unchecked activation is crucial in causing the development and progression of prostate cancer. Second-generation anti-androgen therapies, which primarily focus on targeting the Ligand Binding Domain (LBD) of AR, are effective for most patients. However, the adverse effects pose significant challenges in managing the disease. Furthermore, genetic mutations or the emergence of AR splice variants create an even more complex tumor environment, fostering resistance to these treatments. Natural compounds and their analogs, while showing a lower toxicity profile and a potential for selective AR splice variants inhibition, are constrained by their bioavailability and therapeutic efficacy. Nonetheless, recent breakthroughs in using natural derivatives to target AR and its splice variants have shown promise in treating chemoresistant castration-resistant prostate cancer (CRPC). This review will discuss the role of AR variants, particularly androgen receptor splice variant 7 (AR-V7), in CRPC and investigate the latest findings on how natural compounds and their derivatives target AR and AR splice variants.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"264 ","pages":"Article 108743"},"PeriodicalIF":12.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566770","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

Lipoprotection in cardiovascular diseases 心血管疾病中的血脂保护。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-02 DOI: 10.1016/j.pharmthera.2024.108747

Marcel Benkhoff , Amin Polzin

引用次数: 0

The voltage sensitivity of G-protein coupled receptors: Unraveling molecular mechanisms and physiological implications G 蛋白偶联受体的电压敏感性：揭示分子机制和生理意义。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-01 DOI: 10.1016/j.pharmthera.2024.108741

Marin Boutonnet , Moritz Bünemann , Julie Perroy

{"title":"The voltage sensitivity of G-protein coupled receptors: Unraveling molecular mechanisms and physiological implications","authors":"Marin Boutonnet , Moritz Bünemann , Julie Perroy","doi":"10.1016/j.pharmthera.2024.108741","DOIUrl":"10.1016/j.pharmthera.2024.108741","url":null,"abstract":"<div><div>In the landscape of proteins controlled by membrane voltage (V<sub>m</sub>), like voltage-gated ionotropic channels, the emergence of the voltage sensitivity within the vast family of G-protein coupled receptors (GPCRs) marked a significant milestone at the onset of the 21st century. Since its discovery, extensive research has been devoted to understanding the intricate relationship between V<sub>m</sub> and GPCRs. Approximately 30 GPCRs out of a family comprising more than 800 receptors have been implicated in V<sub>m</sub>-dependent positive and negative regulation. GPCRs stand out as the quintessential regulators of synaptic transmission in neurons, where they encounter substantial variations in V<sub>m</sub>. However, the molecular mechanism underlying the V<sub>m</sub> sensor of GPCRs remains enigmatic, hindered by the scarcity of mutant GPCRs insensitive to V<sub>m</sub> yet functionally intact, impeding a comprehensive understanding of this unique property in physiology. Nevertheless, two decades of dedicated research have furnished numerous insights into the molecular aspects of GPCR V<sub>m</sub>-sensing, accompanied by recently proposed physiological roles as well as pharmacological potential, which we encapsulate in this review. The V<sub>m</sub> sensitivity of GPCRs emerges as a pivotal attribute, shedding light on previously unforeseen roles in synaptic transmission and extending beyond, underscoring its significance in cellular signaling and physiological processes.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"264 ","pages":"Article 108741"},"PeriodicalIF":12.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566772","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

Oxytocin in neurodevelopmental disorders: Autism spectrum disorder and Prader-Willi syndrome 神经发育障碍中的催产素：自闭症谱系障碍和普拉德-威利综合征。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-10-23 DOI: 10.1016/j.pharmthera.2024.108734

Alyssa Josselsohn , Yin Zhao , Danielle Espinoza , Eric Hollander

引用次数: 0

New drug discovery and development from natural products 从天然产品中发现和开发新药物。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-10-23 DOI: 10.1016/j.pharmthera.2024.108733

Michael J. Curtis

引用次数: 0

Natural products that alleviate depression: The putative role of autophagy 缓解抑郁症的天然产品：自噬的潜在作用

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-10-18 DOI: 10.1016/j.pharmthera.2024.108731

Yunfeng Zhou , Fengwei Nan , Qianwen Zhang , Wangjun Xu , Shaojie Fang , Ke Liu , Bingxin Zhao , Hao Han , Xinmei Xie , Changjiang Qin , Xiaobin Pang

{"title":"Natural products that alleviate depression: The putative role of autophagy","authors":"Yunfeng Zhou , Fengwei Nan , Qianwen Zhang , Wangjun Xu , Shaojie Fang , Ke Liu , Bingxin Zhao , Hao Han , Xinmei Xie , Changjiang Qin , Xiaobin Pang","doi":"10.1016/j.pharmthera.2024.108731","DOIUrl":"10.1016/j.pharmthera.2024.108731","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is a common mental disorder that severely disrupts psychosocial function and decreases the quality of life. Although the pathophysiological mechanism underlying MDD is complex and remains unclear, emerging evidence suggests that autophagy dysfunction plays a role in MDD occurrence and progression. Natural products serve as a major source of drug discovery and exert tremendous potential in developing antidepressants. Recently published reports are paying more attention on the autophagy regulatory effect of antidepressant natural products. In this review, we comprehensively discuss the abnormal changes occurred in multiple autophagy stages in MDD patients, and animal and cell models of depression. Importantly, we emphasize the regulatory mechanism of antidepressant natural products on disturbed autophagy, including monomeric compounds, bioactive components, crude extracts, and traditional Chinese medicine formulae. Our comprehensive review suggests that enhancing autophagy might be a novel approach for MDD treatment, and natural products restore autophagy homeostasis to facilitate the renovation of mitochondria, impede neuroinflammation, and enhance neuroplasticity, thereby alleviating depression.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"264 ","pages":"Article 108731"},"PeriodicalIF":12.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455010","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

Role of epigenetic mechanisms in the pathogenesis of chronic respiratory diseases and response to inhaled exposures: From basic concepts to clinical applications 表观遗传机制在慢性呼吸系统疾病发病机制和吸入暴露反应中的作用：从基本概念到临床应用。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-10-18 DOI: 10.1016/j.pharmthera.2024.108732

Renata Z. Jurkowska

{"title":"Role of epigenetic mechanisms in the pathogenesis of chronic respiratory diseases and response to inhaled exposures: From basic concepts to clinical applications","authors":"Renata Z. Jurkowska","doi":"10.1016/j.pharmthera.2024.108732","DOIUrl":"10.1016/j.pharmthera.2024.108732","url":null,"abstract":"<div><div>Epigenetic modifications are chemical groups in our DNA (and chromatin) that determine which genes are active and which are shut off. Importantly, they integrate environmental signals to direct cellular function. Upon chronic environmental exposures, the epigenetic signature of lung cells gets altered, triggering aberrant gene expression programs that can lead to the development of chronic lung diseases. In addition to driving disease, epigenetic marks can serve as attractive lung disease biomarkers, due to early onset, disease specificity, and stability, warranting the need for more epigenetic research in the lung field.</div><div>Despite substantial progress in mapping epigenetic alterations (mostly DNA methylation) in chronic lung diseases, the molecular mechanisms leading to their establishment are largely unknown. This review is meant as a guide for clinicians and lung researchers interested in epigenetic regulation with a focus on DNA methylation. It provides a short introduction to the main epigenetic mechanisms (DNA methylation, histone modifications and non-coding RNA) and the machinery responsible for their establishment and removal. It presents examples of epigenetic dysregulation across a spectrum of chronic lung diseases and discusses the current state of epigenetic therapies. Finally, it introduces the concept of epigenetic editing, an exciting novel approach to dissecting the functional role of epigenetic modifications. The promise of this emerging technology for the functional study of epigenetic mechanisms in cells and its potential future use in the clinic is further discussed.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"264 ","pages":"Article 108732"},"PeriodicalIF":12.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455011","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

Metrnl as a secreted protein: Discovery and cardiovascular research 作为分泌蛋白的 Metrnl：发现与心血管研究

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-10-12 DOI: 10.1016/j.pharmthera.2024.108730

Zhu-Wei Miao , Jin Chen , Can-Xin Chen , Si-Li Zheng , Huan-Yu Zhao , Chao-Yu Miao

{"title":"Metrnl as a secreted protein: Discovery and cardiovascular research","authors":"Zhu-Wei Miao , Jin Chen , Can-Xin Chen , Si-Li Zheng , Huan-Yu Zhao , Chao-Yu Miao","doi":"10.1016/j.pharmthera.2024.108730","DOIUrl":"10.1016/j.pharmthera.2024.108730","url":null,"abstract":"<div><div>Secreted proteins have gained more and more attentions, since they can become therapeutic targets, drugs and biomarkers for prevention, diagnosis and treatment of disease and aging. In 2014, Metrnl (also named Meteorin-like, Cometin, Subfatin, Interleukin-39, Interleukin-41, Meteorin-β, and Metrn-β/Metrnβ), as a novel secreted protein released from a certain tissue, was reported by us and others. During the past decade, the number of articles on Metrnl has continued to increase. Different sources of Metrnl have been described with different functions, including Metrnl as an adipokine for insulin sensitization, a cardiokine against cardiac hypertrophy and dysfunction, an endothelium-derived factor against endothelial dysfunction and atherosclerosis, etc. Especially, we show that endothelial Metrnl is a major source for circulating Metrnl levels. Meanwhile, lots of clinical studies have investigated the relationship between blood Metrnl levels and metabolic, inflammatory and cardiovascular diseases. Metrnl appears a protective factor and a promising therapeutic target and/or drug against these diseases, given the relatively consistent conclusion from the preclinical studies. In addition to graphically demonstrating the role of Metrnl in various organs and diseases, this review will mainly describe the discovery of Metrnl, summarize the role of Metrnl in cardiovascular system that is a recently major progress in Metrnl research, and highlight several perspectives for future basic and translational research. Also, we suggest using one name Metrnl instead of other multiple names for the same protein.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"263 ","pages":"Article 108730"},"PeriodicalIF":12.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455009","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 selective autophagy in CNS disorders by small-molecule compounds 用小分子化合物靶向中枢神经系统疾病中的选择性自噬。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-10-12 DOI: 10.1016/j.pharmthera.2024.108729

Yanrong Zheng , Zhuchen Zhou , Mengting Liu, Zhong Chen

{"title":"Targeting selective autophagy in CNS disorders by small-molecule compounds","authors":"Yanrong Zheng , Zhuchen Zhou , Mengting Liu, Zhong Chen","doi":"10.1016/j.pharmthera.2024.108729","DOIUrl":"10.1016/j.pharmthera.2024.108729","url":null,"abstract":"<div><div>Autophagy functions as the primary cellular mechanism for clearing unwanted intracellular contents. Emerging evidence suggests that the selective elimination of intracellular organelles through autophagy, compared to the increased bulk autophagic flux, is crucial for the pathological progression of central nervous system (CNS) disorders. Notably, autophagic removal of mitochondria, known as mitophagy, is well-understood in an unhealthy brain. Accumulated data indicate that selective autophagy of other substrates, including protein aggregates, liposomes, and endoplasmic reticulum, plays distinctive roles in various pathological stages. Despite variations in substrates, the molecular mechanisms governing selective autophagy can be broadly categorized into two types: ubiquitin-dependent and -independent pathways, both of which can be subjected to regulation by small-molecule compounds. Notably, natural products provide the remarkable possibility for future structural optimization to regulate the highly selective autophagic clearance of diverse substrates. In this context, we emphasize the selectivity of autophagy in regulating CNS disorders and provide an overview of chemical compounds capable of modulating selective autophagy in these disorders, along with the underlying mechanisms. Further exploration of the functions of these compounds will in turn advance our understanding of autophagic contributions to brain disorders and illuminate precise therapeutic strategies for these diseases.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"263 ","pages":"Article 108729"},"PeriodicalIF":12.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455012","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

The TRPC5 receptor as pharmacological target for pain and metabolic disease 将 TRPC5 受体作为治疗疼痛和代谢疾病的药理靶点。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-10-09 DOI: 10.1016/j.pharmthera.2024.108727

Pragyanshu Khare , Jagdish Chand , Alexandra Ptakova , Renato Liguori , Fulvia Ferrazzi , Mahendra Bishnoi , Viktorie Vlachova , Katharina Zimmermann

{"title":"The TRPC5 receptor as pharmacological target for pain and metabolic disease","authors":"Pragyanshu Khare , Jagdish Chand , Alexandra Ptakova , Renato Liguori , Fulvia Ferrazzi , Mahendra Bishnoi , Viktorie Vlachova , Katharina Zimmermann","doi":"10.1016/j.pharmthera.2024.108727","DOIUrl":"10.1016/j.pharmthera.2024.108727","url":null,"abstract":"<div><div>The transient receptor potential canonical (TRPC) channels are a group of highly homologous nonselective cation channels from the larger TRP channel family. They have the ability to form homo- and heteromers with varying degrees of calcium (Ca<sup>2+</sup>) permeability and signalling properties. TRPC5 is the one cold-sensitive among them and likewise facilitates the influx of extracellular Ca<sup>2+</sup> into cells to modulate neuronal depolarization and integrate various intracellular signalling pathways. Recent research with cryo-electron microscopy revealed its structure, along with clear insight into downstream signalling and protein-protein interaction sites. Investigations using global and conditional deficient mice revealed the involvement of TRPC5 in metabolic diseases, energy balance, thermosensation and conditions such as osteoarthritis, rheumatoid arthritis, and inflammatory pain including opioid-induced hyperalgesia and hyperalgesia following tooth decay and pulpitis. This review provides an update on recent advances in our understanding of the role of TRPC5 with focus on metabolic diseases and pain.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"263 ","pages":"Article 108727"},"PeriodicalIF":12.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387016","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