Physiological reviews最新文献_第3页

Deconstructing the GWAS library - Next Generation GWAS 解构GWAS库-下一代GWAS

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-05-23 DOI: 10.1152/physrev.00025.2024

Weirui Zhang, Svenja Koslowski, Marouane Benzaki, Chang Jie Mick Lee, Yike Zhu, Michelle C.E Mak, Yonglin Zhu, Shaun S.E Loong, Guillaume Lettre, Chukwuemeka George Anene-Nzelu, Roger Foo

引用次数: 0

Immunotherapy for atherosclerosis 动脉粥样硬化的免疫治疗

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-05-21 DOI: 10.1152/physrev.00016.2024

Claudia Monaco, Coleen A. McNamara, Bram Slütter, Amanda C. Foks, Stefan Bekiranov, Willem J.M. Mulder, Isabel Gonçalves, Esther Lutgens

引用次数: 0

Cysteine-based redox sensors in the cardiovascular system - from identification to physiology and drug discovery. 心血管系统中基于半胱氨酸的氧化还原传感器——从鉴定到生理学和药物发现。

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-05-08 DOI: 10.1152/physrev.00051.2024

Joseph R Burgoyne,Philip Eaton

引用次数: 0

Central nervous system mechanisms of salt-sensitive hypertension 盐敏感性高血压的中枢神经系统机制

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-05-02 DOI: 10.1152/physrev.00035.2024

Yumei Feng Earley, Shiyue Pan, Himanshu Verma, Haifeng Zheng, Adriana Alviter Plata, Jasenka Zubcevic, Frans H.H. Leenen

引用次数: 0

Uterine Fibroids 子宫肌瘤

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-04-11 DOI: 10.1152/physrev.00010.2024

Serdar E Bulun, Ping Yin, Jian-Jun Wei, Azna Zuberi, Takashi Iizuka, Takuma Suzuki, Priyanka Saini, Jyoti Goad, J. Brandon Parker, Mazhar Adli, Thomas Boyer, Debabrata Chakravarti, Aleksandar Rajkovic

引用次数: 0

TPCs: From plant to human. TPCs：从植物到人类。

IF 29.9 1区医学

Physiological reviews Pub Date : 2025-04-03 DOI: 10.1152/physrev.00044.2024

Yvonne Eileen Klingl, Arnas Petrauskas, Dawid Jaślan, Christian Grimm

{"title":"TPCs: From plant to human.","authors":"Yvonne Eileen Klingl, Arnas Petrauskas, Dawid Jaślan, Christian Grimm","doi":"10.1152/physrev.00044.2024","DOIUrl":"https://doi.org/10.1152/physrev.00044.2024","url":null,"abstract":"In 2005, the Arabidopsis thaliana two-pore channel TPC1 channel was identified as a vacuolar Ca²⁺-release channel. In 2009 three independent groups published studies on mammalian TPCs as NAADP-activated endolysosomal Ca2+ release channels, results that were eventually challenged by two other groups, claiming mammalian TPCs to be PI(3,5)P2 activated Na+ channels. By now this dispute seems to have been largely reconciled. Lipophilic small molecule agonists of TPC2, mimicking either the NAADP or the PI(3,5)P2 mode of channel activation, revealed, together with structural evidence, that TPC2 can change its selectivity for Ca2+ versus Na+ in a ligand-dependent fashion (N- versus P-type activation). Furthermore, NAADP-binding proteins, JPT2 and Lsm12 were discovered, corroborating the hypothesis that NAADP activation of TPCs only works in the presence of these auxiliary NAADP-binding proteins. Pathophysiologically, loss or gain of function of TPCs has effects on autophagy, exocytosis, endocytosis, and intracellular trafficking, e.g., LDL cholesterol trafficking leading to fatty liver disease or viral and bacterial toxin trafficking, corroborating roles of TPCs in infectious diseases such as Ebola or Covid19. Defects in trafficking of EGFR and 1-integrin suggested roles in cancer. In neurodegenerative lysosomal storage disease models, P-type activation of TPC2 was found to have beneficial effects on both in vitro and in vivo hallmarks of Niemann- Pick disease type C1, Batten disease, and Mucolipidosis type IV. Here, we cover the latest on structure, function, physiology, and pathophysiology of these channels with a focus initially on plant followed by mammalian TPCs, and we discuss their potential as drug targets, including currently available pharmacology.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":""},"PeriodicalIF":29.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773080","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

A Comprehensive View of Muscle Glucose Uptake: Regulation by Insulin, Contractile Activity and Exercise 肌肉葡萄糖摄取的综合观点：胰岛素、收缩活动和运动的调节

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-04-02 DOI: 10.1152/physrev.00033.2024

Erik A. Richter, Philip J. Bilan, Amira Klip

引用次数: 0

Axon initial segment structure and function in health and disease. 健康与疾病中的轴突起始节结构和功能

IF 29.9 1区医学

Physiological reviews Pub Date : 2025-04-01 Epub Date: 2024-10-31 DOI: 10.1152/physrev.00030.2024

Paul M Jenkins, Kevin J Bender

{"title":"Axon initial segment structure and function in health and disease.","authors":"Paul M Jenkins, Kevin J Bender","doi":"10.1152/physrev.00030.2024","DOIUrl":"10.1152/physrev.00030.2024","url":null,"abstract":"At the simplest level, neurons are structured to integrate synaptic input and perform computational transforms on that input, converting it into an action potential (AP) code. This process, converting synaptic input into AP output, typically occurs in a specialized region of the axon termed the axon initial segment (AIS). The AIS, as its name implies, is often contained to the first section of axon abutted to the soma and is home to a dizzying array of ion channels, attendant scaffolding proteins, intracellular organelles, extracellular proteins, and, in some cases, synapses. The AIS serves multiple roles as the final arbiter for determining if inputs are sufficient to evoke APs, as a gatekeeper that physically separates the somatodendritic domain from the axon proper, and as a regulator of overall neuronal excitability, dynamically tuning its size to best suit the needs of parent neurons. These complex roles have received considerable attention from experimentalists and theoreticians alike. Here, we review recent advances in our understanding of the AIS and its role in neuronal integration and polarity in health and disease.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"765-801"},"PeriodicalIF":29.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546860","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

Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions. 心脏病理生理学中的纳米域 cAMP 信号：开发靶向治疗干预的潜力。

IF 29.9 1区医学

Physiological reviews Pub Date : 2025-04-01 Epub Date: 2024-08-08 DOI: 10.1152/physrev.00013.2024

Manuela Zaccolo, Duangnapa Kovanich

{"title":"Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.","authors":"Manuela Zaccolo, Duangnapa Kovanich","doi":"10.1152/physrev.00013.2024","DOIUrl":"10.1152/physrev.00013.2024","url":null,"abstract":"The 3',5'-cyclic adenosine monophosphate (cAMP) mediates the effects of sympathetic stimulation on the rate and strength of cardiac contraction. Beyond this pivotal role, in cardiac myocytes cAMP also orchestrates a diverse array of reactions to various stimuli. To ensure specificity of response, the cAMP signaling pathway is intricately organized into multiple, spatially confined, subcellular domains, each governing a distinct cellular function. In this review, we describe the molecular components of the cAMP signaling pathway with a specific focus on adenylyl cyclases, A-kinase anchoring proteins, and phosphodiesterases. We discuss how they are organized inside the intracellular space and how they achieve exquisite regulation of signaling within nanometer-size domains. We delineate the key experimental findings that lead to the current model of compartmentalized cAMP signaling, and we offer an overview of our present understanding of how cAMP nanodomains are structured and regulated within cardiac myocytes. Furthermore, we discuss how compartmentalized cAMP signaling is affected in cardiac disease and consider the potential therapeutic opportunities arising from understanding such organization. By exploiting the nuances of compartmentalized cAMP signaling, novel and more effective therapeutic strategies for managing cardiac conditions may emerge. Finally, we highlight the unresolved questions and hurdles that must be addressed to translate these insights into interventions that may benefit patients.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"541-591"},"PeriodicalIF":29.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902635","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

Biomarkers of aging: from molecules and surrogates to physiology and function 衰老的生物标志物：从分子和替代物到生理和功能

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-03-20 DOI: 10.1152/physrev.00045.2024

Regula Furrer, Christoph Handschin

引用次数: 0