Physiological reviews最新文献_第10页

CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond. CGRP 生理、药理和治疗目标：偏头痛及其他。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-04-01 Epub Date: 2022-12-01 DOI: 10.1152/physrev.00059.2021

Andrew F Russo, Debbie L Hay

{"title":"CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.","authors":"Andrew F Russo, Debbie L Hay","doi":"10.1152/physrev.00059.2021","DOIUrl":"10.1152/physrev.00059.2021","url":null,"abstract":"Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse physiological functions. Its two isoforms (α and β) are widely expressed throughout the body in sensory neurons as well as in other cell types, such as motor neurons and neuroendocrine cells. CGRP acts via at least two G protein-coupled receptors that form unusual complexes with receptor activity-modifying proteins. These are the CGRP receptor and the AMY1 receptor; in rodents, additional receptors come into play. Although CGRP is known to produce many effects, the precise molecular identity of the receptor(s) that mediates CGRP effects is seldom clear. Despite the many enigmas still in CGRP biology, therapeutics that target the CGRP axis to treat or prevent migraine are a bench-to-bedside success story. This review provides a contextual background on the regulation and sites of CGRP expression and CGRP receptor pharmacology. The physiological actions of CGRP in the nervous system are discussed, along with updates on CGRP actions in the cardiovascular, pulmonary, gastrointestinal, immune, hematopoietic, and reproductive systems and metabolic effects of CGRP in muscle and adipose tissues. We cover how CGRP in these systems is associated with disease states, most notably migraine. In this context, we discuss how CGRP actions in both the peripheral and central nervous systems provide a basis for therapeutic targeting of CGRP in migraine. Finally, we highlight potentially fertile ground for the development of additional therapeutics and combinatorial strategies that could be designed to modulate CGRP signaling for migraine and other diseases.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 2","pages":"1565-1644"},"PeriodicalIF":33.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9871059","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

The physiological functions of human peroxisomes. 人体过氧化物酶体的生理功能。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-01-01 DOI: 10.1152/physrev.00051.2021

Ronald J A Wanders, Myriam Baes, Daniela Ribeiro, Sacha Ferdinandusse, Hans R Waterham

{"title":"The physiological functions of human peroxisomes.","authors":"Ronald J A Wanders, Myriam Baes, Daniela Ribeiro, Sacha Ferdinandusse, Hans R Waterham","doi":"10.1152/physrev.00051.2021","DOIUrl":"https://doi.org/10.1152/physrev.00051.2021","url":null,"abstract":"Peroxisomes are subcellular organelles that play a central role in human physiology by catalyzing a range of unique metabolic functions. The importance of peroxisomes for human health is exemplified by the existence of a group of usually severe diseases caused by an impairment in one or more peroxisomal functions. Among others these include the Zellweger spectrum disorders, X-linked adrenoleukodystrophy, and Refsum disease. To fulfill their role in metabolism, peroxisomes require continued interaction with other subcellular organelles including lipid droplets, lysosomes, the endoplasmic reticulum, and mitochondria. In recent years it has become clear that the metabolic alliance between peroxisomes and other organelles requires the active participation of tethering proteins to bring the organelles physically closer together, thereby achieving efficient transfer of metabolites. This review intends to describe the current state of knowledge about the metabolic role of peroxisomes in humans, with particular emphasis on the metabolic partnership between peroxisomes and other organelles and the consequences of genetic defects in these processes. We also describe the biogenesis of peroxisomes and the consequences of the multiple genetic defects therein. In addition, we discuss the functional role of peroxisomes in different organs and tissues and include relevant information derived from model systems, notably peroxisomal mouse models. Finally, we pay particular attention to a hitherto underrated role of peroxisomes in viral infections.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"957-1024"},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10400622","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

Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum. 发育性和癫痫性脑病：从遗传异质性到表型连续性。

IF 29.9 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-08-11 DOI: 10.1152/physrev.00063.2021

Renzo Guerrini, Valerio Conti, Massimo Mantegazza, Simona Balestrini, Aristea S Galanopoulou, Fabio Benfenati

{"title":"Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.","authors":"Renzo Guerrini, Valerio Conti, Massimo Mantegazza, Simona Balestrini, Aristea S Galanopoulou, Fabio Benfenati","doi":"10.1152/physrev.00063.2021","DOIUrl":"10.1152/physrev.00063.2021","url":null,"abstract":"Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by early-onset, often severe epileptic seizures and EEG abnormalities on a background of developmental impairment that tends to worsen as a consequence of epilepsy. DEEs may result from both nongenetic and genetic etiologies. Genetic DEEs have been associated with mutations in many genes involved in different functions including cell migration, proliferation, and organization, neuronal excitability, and synapse transmission and plasticity. Functional studies performed in different animal models and clinical trials on patients have contributed to elucidate pathophysiological mechanisms underlying many DEEs and have explored the efficacy of different treatments. Here, we provide an extensive review of the phenotypic spectrum included in the DEEs and of the genetic determinants and pathophysiological mechanisms underlying these conditions. We also provide a brief overview of the most effective treatment now available and of the emerging therapeutic approaches.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"433-513"},"PeriodicalIF":29.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296409","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

A systematic review of the biological mediators of fat taste and smell. 脂肪味觉和嗅觉的生物介质的系统综述。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-01-01 DOI: 10.1152/physrev.00061.2021

Rosario B Jaime-Lara, Brianna E Brooks, Carlotta Vizioli, Mari Chiles, Nafisa Nawal, Rodrigo S E Ortiz-Figueroa, Alicia A Livinski, Khushbu Agarwal, Claudia Colina-Prisco, Natalia Iannarino, Aliya Hilmi, Hugo A Tejeda, Paule V Joseph

{"title":"A systematic review of the biological mediators of fat taste and smell.","authors":"Rosario B Jaime-Lara, Brianna E Brooks, Carlotta Vizioli, Mari Chiles, Nafisa Nawal, Rodrigo S E Ortiz-Figueroa, Alicia A Livinski, Khushbu Agarwal, Claudia Colina-Prisco, Natalia Iannarino, Aliya Hilmi, Hugo A Tejeda, Paule V Joseph","doi":"10.1152/physrev.00061.2021","DOIUrl":"https://doi.org/10.1152/physrev.00061.2021","url":null,"abstract":"Taste and smell play a key role in our ability to perceive foods. Overconsumption of highly palatable energy-dense foods can lead to increased caloric intake and obesity. Thus there is growing interest in the study of the biological mediators of fat taste and associated olfaction as potential targets for pharmacologic and nutritional interventions in the context of obesity and health. The number of studies examining mechanisms underlying fat taste and smell has grown rapidly in the last 5 years. Therefore, the purpose of this systematic review is to summarize emerging evidence examining the biological mechanisms of fat taste and smell. A literature search was conducted of studies published in English between 2014 and 2021 in adult humans and animal models. Database searches were conducted using PubMed, EMBASE, Scopus, and Web of Science for key terms including fat/lipid, taste, and olfaction. Initially, 4,062 articles were identified through database searches, and a total of 84 relevant articles met inclusion and exclusion criteria and are included in this review. Existing literature suggests that there are several proteins integral to fat chemosensation, including cluster of differentiation 36 (CD36) and G protein-coupled receptor 120 (GPR120). This systematic review will discuss these proteins and the signal transduction pathways involved in fat detection. We also review neural circuits, key brain regions, ingestive cues, postingestive signals, and genetic polymorphism that play a role in fat perception and consumption. Finally, we discuss the role of fat taste and smell in the context of eating behavior and obesity.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"855-918"},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10079977","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: 7

Evolution of the diagnostic value of "the sugar of the blood": hitting the sweet spot to identify alterations in glucose dynamics. 血糖 "诊断价值的演变：找到识别葡萄糖动态变化的最佳点。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-05-30 DOI: 10.1152/physrev.00015.2022

Faidon Magkos, Dominic N Reeds, Bettina Mittendorfer

引用次数: 0

Ion channels and channelopathies in glomeruli. 肾小球中的离子通道和通道病。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-08-25 DOI: 10.1152/physrev.00013.2022

Alexander Staruschenko, Rong Ma, Oleg Palygin, Stuart E Dryer

{"title":"Ion channels and channelopathies in glomeruli.","authors":"Alexander Staruschenko, Rong Ma, Oleg Palygin, Stuart E Dryer","doi":"10.1152/physrev.00013.2022","DOIUrl":"10.1152/physrev.00013.2022","url":null,"abstract":"An essential step in renal function entails the formation of an ultrafiltrate that is delivered to the renal tubules for subsequent processing. This process, known as glomerular filtration, is controlled by intrinsic regulatory systems and by paracrine, neuronal, and endocrine signals that converge onto glomerular cells. In addition, the characteristics of glomerular fluid flow, such as the glomerular filtration rate and the glomerular filtration fraction, play an important role in determining blood flow to the rest of the kidney. Consequently, disease processes that initially affect glomeruli are the most likely to lead to end-stage kidney failure. The cells that comprise the glomerular filter, especially podocytes and mesangial cells, express many different types of ion channels that regulate intrinsic aspects of cell function and cellular responses to the local environment, such as changes in glomerular capillary pressure. Dysregulation of glomerular ion channels, such as changes in TRPC6, can lead to devastating glomerular diseases, and a number of channels, including TRPC6, TRPC5, and various ionotropic receptors, are promising targets for drug development. This review discusses glomerular structure and glomerular disease processes. It also describes the types of plasma membrane ion channels that have been identified in glomerular cells, the physiological and pathophysiological contexts in which they operate, and the pathways by which they are regulated and dysregulated. The contributions of these channels to glomerular disease processes, such as focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, as well as the development of drugs that target these channels are also discussed.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"787-854"},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9286240","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: 10

Protease-activated receptors in health and disease. 健康和疾病中的蛋白酶激活受体。

IF 29.9 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-07-28 DOI: 10.1152/physrev.00044.2021

Chloe J Peach, Laura E Edgington-Mitchell, Nigel W Bunnett, Brian L Schmidt

{"title":"Protease-activated receptors in health and disease.","authors":"Chloe J Peach, Laura E Edgington-Mitchell, Nigel W Bunnett, Brian L Schmidt","doi":"10.1152/physrev.00044.2021","DOIUrl":"10.1152/physrev.00044.2021","url":null,"abstract":"Proteases are signaling molecules that specifically control cellular functions by cleaving protease-activated receptors (PARs). The four known PARs are members of the large family of G protein-coupled receptors. These transmembrane receptors control most physiological and pathological processes and are the target of a large proportion of therapeutic drugs. Signaling proteases include enzymes from the circulation; from immune, inflammatory epithelial, and cancer cells; as well as from commensal and pathogenic bacteria. Advances in our understanding of the structure and function of PARs provide insights into how diverse proteases activate these receptors to regulate physiological and pathological processes in most tissues and organ systems. The realization that proteases and PARs are key mediators of disease, coupled with advances in understanding the atomic level structure of PARs and their mechanisms of signaling in subcellular microdomains, has spurred the development of antagonists, some of which have advanced to the clinic. Herein we review the discovery, structure, and function of this receptor system, highlight the contribution of PARs to homeostatic control, and discuss the potential of PAR antagonists for the treatment of major diseases.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"717-785"},"PeriodicalIF":29.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9602459","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

Cortical-subcortical interactions in goal-directed behavior. 目标定向行为中的皮层-皮层下相互作用

IF 29.9 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-06-30 DOI: 10.1152/physrev.00048.2021

K Guadalupe Cruz, Yi Ning Leow, Nhat Minh Le, Elie Adam, Rafiq Huda, Mriganka Sur

{"title":"Cortical-subcortical interactions in goal-directed behavior.","authors":"K Guadalupe Cruz, Yi Ning Leow, Nhat Minh Le, Elie Adam, Rafiq Huda, Mriganka Sur","doi":"10.1152/physrev.00048.2021","DOIUrl":"10.1152/physrev.00048.2021","url":null,"abstract":"Flexibly selecting appropriate actions in response to complex, ever-changing environments requires both cortical and subcortical regions, which are typically described as participating in a strict hierarchy. In this traditional view, highly specialized subcortical circuits allow for efficient responses to salient stimuli, at the cost of adaptability and context specificity, which are attributed to the neocortex. Their interactions are often described as the cortex providing top-down command signals for subcortical structures to implement; however, as available technologies develop, studies increasingly demonstrate that behavior is represented by brainwide activity and that even subcortical structures contain early signals of choice, suggesting that behavioral functions emerge as a result of different regions interacting as truly collaborative networks. In this review, we discuss the field's evolving understanding of how cortical and subcortical regions in placental mammals interact cooperatively, not only via top-down cortical-subcortical inputs but through bottom-up interactions, especially via the thalamus. We describe our current understanding of the circuitry of both the cortex and two exemplar subcortical structures, the superior colliculus and striatum, to identify which information is prioritized by which regions. We then describe the functional circuits these regions form with one another, and the thalamus, to create parallel loops and complex networks for brainwide information flow. Finally, we challenge the classic view that functional modules are contained within specific brain regions; instead, we propose that certain regions prioritize specific types of information over others, but the subnetworks they form, defined by their anatomical connections and functional dynamics, are the basis of true specialization.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"347-389"},"PeriodicalIF":29.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9401464","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

The choroid plexus: a missing link in our understanding of brain development and function. 脉络丛：我们了解大脑发育和功能的一个缺失环节。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-09-29 DOI: 10.1152/physrev.00060.2021

Norman R Saunders, Katarzyna M Dziegielewska, Ryann M Fame, Maria K Lehtinen, Shane A Liddelow

{"title":"The choroid plexus: a missing link in our understanding of brain development and function.","authors":"Norman R Saunders, Katarzyna M Dziegielewska, Ryann M Fame, Maria K Lehtinen, Shane A Liddelow","doi":"10.1152/physrev.00060.2021","DOIUrl":"10.1152/physrev.00060.2021","url":null,"abstract":"Studies of the choroid plexus lag behind those of the more widely known blood-brain barrier, despite a much longer history. This review has two overall aims. The first is to outline long-standing areas of research where there are unanswered questions, such as control of cerebrospinal fluid (CSF) secretion and blood flow. The second aim is to review research over the past 10 years where the focus has shifted to the idea that there are choroid plexuses located in each of the brain's ventricles that make specific contributions to brain development and function through molecules they generate for delivery via the CSF. These factors appear to be particularly important for aspects of normal brain growth. Most research carried out during the twentieth century dealt with the choroid plexus, a brain barrier interface making critical contributions to the composition and stability of the brain's internal environment throughout life. More recent research in the twenty-first century has shown the importance of choroid plexus-generated CSF in neurogenesis, influence of sex and other hormones on choroid plexus function, and choroid plexus involvement in circadian rhythms and sleep. The advancement of technologies to facilitate delivery of brain-specific therapies via the CSF to treat neurological disorders is a rapidly growing area of research. Conversely, understanding the basic mechanisms and implications of how maternal drug exposure during pregnancy impacts the developing brain represents another key area of research.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"919-956"},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9101150","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: 8

Clonal hematopoiesis, somatic mosaicism, and age-associated disease. 克隆造血、体细胞嵌合和年龄相关疾病。

IF 29.9 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-09-01 DOI: 10.1152/physrev.00004.2022

Megan A Evans, Kenneth Walsh

{"title":"Clonal hematopoiesis, somatic mosaicism, and age-associated disease.","authors":"Megan A Evans, Kenneth Walsh","doi":"10.1152/physrev.00004.2022","DOIUrl":"10.1152/physrev.00004.2022","url":null,"abstract":"Somatic mosaicism, the occurrence of multiple genetically distinct cell clones within the same tissue, is an evitable consequence of human aging. The hematopoietic system is no exception to this, where studies have revealed the presence of expanded blood cell clones carrying mutations in preleukemic driver genes and/or genetic alterations in chromosomes. This phenomenon is referred to as clonal hematopoiesis and is remarkably prevalent in elderly individuals. While clonal hematopoiesis represents an early step toward a hematological malignancy, most individuals will never develop blood cancer. Somewhat unexpectedly, epidemiological studies have found that clonal hematopoiesis is associated with an increase in the risk of all-cause mortality and age-related disease, particularly in the cardiovascular system. Studies using murine models of clonal hematopoiesis have begun to shed light on this relationship, suggesting that driver mutations in mature blood cells can causally contribute to aging and disease by augmenting inflammatory processes. Here we provide an up-to-date review of clonal hematopoiesis within the context of somatic mosaicism and aging and describe recent epidemiological studies that have reported associations with age-related disease. We will also discuss the experimental studies that have provided important mechanistic insight into how driver mutations promote age-related disease and how this knowledge could be leveraged to treat individuals with clonal hematopoiesis.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"649-716"},"PeriodicalIF":29.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10702900","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