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Protein phosphatases in metabolic dysfunction-associated steatotic liver disease: emerging mechanisms and therapeutic strategies 蛋白质磷酸酶与代谢功能障碍相关的脂肪变性肝病：新出现的机制和治疗策略
IF 1.9
Current Opinion in Physiology Pub Date : 2025-09-19 DOI: 10.1016/j.cophys.2025.100860
Shaira Gail Santos , Khaja Shameem Mohammed Abdul , Nicole H Purcell
{"title":"Protein phosphatases in metabolic dysfunction-associated steatotic liver disease: emerging mechanisms and therapeutic strategies","authors":"Shaira Gail Santos ,&nbsp;Khaja Shameem Mohammed Abdul ,&nbsp;Nicole H Purcell","doi":"10.1016/j.cophys.2025.100860","DOIUrl":"10.1016/j.cophys.2025.100860","url":null,"abstract":"<div><div>Metabolic dysfunction–associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease globally, with its severe form, metabolic dysfunction–associated steatohepatitis (MASH), increasing the risk of fibrosis, cirrhosis, and hepatocellular carcinoma. Despite its prevalence, there are limited FDA-approved therapies for MASLD, underscoring the need for novel treatment strategies. Protein phosphatases play critical roles in MASLD pathogenesis as key regulators of metabolic and inflammatory pathways. This review highlights specific phosphatases that are crucial in insulin signaling, lipid metabolism, inflammation, and fibrosis within the liver. While some phosphatases exacerbate disease progression by promoting liver dysfunction, others exhibit protective effects, suggesting potential as therapeutic targets. Altering phosphatase activity may reduce steatosis, improve insulin sensitivity, and alleviate fibrosis. Continued research is essential for developing selective modulators with minimal off-target effects, with the goal of identifying therapeutic approaches to prevent or reverse MASLD progression.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100860"},"PeriodicalIF":1.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The link between circadian disruption and Alzheimer’s disease and related dementias: insights from peripheral inflammation 昼夜节律紊乱与阿尔茨海默病及相关痴呆之间的联系：来自外周炎症的见解
IF 1.9
Current Opinion in Physiology Pub Date : 2025-09-12 DOI: 10.1016/j.cophys.2025.100859
Carmalena V Cordi , Jennifer M Hurley
{"title":"The link between circadian disruption and Alzheimer’s disease and related dementias: insights from peripheral inflammation","authors":"Carmalena V Cordi ,&nbsp;Jennifer M Hurley","doi":"10.1016/j.cophys.2025.100859","DOIUrl":"10.1016/j.cophys.2025.100859","url":null,"abstract":"<div><div>Circadian rhythms are essential for maintaining physiological homeostasis, influencing biological processes from the sleep–wake cycle to metabolism and immune responses. Disruption of these rhythms is increasingly linked to the pathogenesis of Alzheimer’s disease and related dementias (ADRDs), conditions characterized by cognitive decline and neuropsychiatric symptoms through various pathways, including increases in inflammation. While many studies link the effects of circadian disruption on neuroinflammation to ADRDs, this review explores the potential link between the circadian disruption of peripheral inflammation and ADRDs. We discuss the evidence of how circadian misalignment can exacerbate neuroinflammation through the activation of the peripheral immune system. We further examine the role of peripheral factors such as insulin dysregulation, melatonin levels, and gut microbiome imbalances in amplifying these peripheral inflammatory responses. These data underscore the significance of circadian regulation in maintaining immune homeostasis, highlighting potential therapeutic avenues for mitigating ADRDs through the restoration of circadian integrity.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100859"},"PeriodicalIF":1.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protein phosphatase 2A as a therapeutic target in pancreatic cancer: past insights, recent advances, and future directions 蛋白磷酸酶2A作为胰腺癌的治疗靶点：过去的见解，最近的进展和未来的方向
IF 1.9
Current Opinion in Physiology Pub Date : 2025-08-28 DOI: 10.1016/j.cophys.2025.100849
Vidhi M Shah , Rosalie C Sears
{"title":"Protein phosphatase 2A as a therapeutic target in pancreatic cancer: past insights, recent advances, and future directions","authors":"Vidhi M Shah ,&nbsp;Rosalie C Sears","doi":"10.1016/j.cophys.2025.100849","DOIUrl":"10.1016/j.cophys.2025.100849","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an 8% five-year survival rate. KRAS, the major oncogenic driver, triggers several phosphorylation cascades, making phosphatases, particularly protein phosphatase 2A (PP2A), which accounts for 50–70% of cellular phosphatase activity, a critical regulator. Through association with multiple regulatory subunits, PP2A modulates both tumor-suppressive and tumor-promoting functions. The tumor-suppressive function is often inhibited in PDAC by endogenous inhibitors like SET and CIP2A, which are frequently upregulated. This review examines the multifaceted roles of PP2A in PDAC, with a focus on its published roles in KRAS-MYC signaling, DNA damage response, and epithelial-to-mesenchymal transition, as well as current and emerging therapeutic strategies aimed at modulating PP2A activity.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100849"},"PeriodicalIF":1.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanisms of microRNA trafficking to mitochondria in the heart microRNA转运至心脏线粒体的机制
IF 1.9
Current Opinion in Physiology Pub Date : 2025-08-08 DOI: 10.1016/j.cophys.2025.100848
Diego Quiroga , Rachel Daniel , Samarjit Das
{"title":"Mechanisms of microRNA trafficking to mitochondria in the heart","authors":"Diego Quiroga ,&nbsp;Rachel Daniel ,&nbsp;Samarjit Das","doi":"10.1016/j.cophys.2025.100848","DOIUrl":"10.1016/j.cophys.2025.100848","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are essential post-transcriptional regulators of gene expression, and accumulating evidence supports their presence and function within mitochondria. These mitochondrial microRNAs (MitomiRs) modulate key processes such as oxidative phosphorylation, ATP production, calcium homeostasis, and reactive oxygen species balance in cardiac tissue. Despite growing recognition of their importance, the mechanisms governing miRNA trafficking to mitochondria remain incompletely understood. This review explores the current knowledge on miRNA biogenesis, mitochondrial import pathways — including the roles of Argonaute 2 (AGO2), the Translocase of the Outer/Inner Mitochondrial Membrane (TOM/TIM) complexes, and Polynucleotide Phosphorylase (PNPase) — and the regulatory impact of specific MitomiRs, such as miR-181c, miR-210, miR-378, let-7b, and miR-1. Understanding how these molecules influence mitochondrial function provides insight into their therapeutic potential in cardiovascular disease.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100848"},"PeriodicalIF":1.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Noncoding RNA in cancer: pathogenesis to therapeutic targets 非编码RNA在癌症中的作用：发病机制和治疗靶点
IF 2.5
Current Opinion in Physiology Pub Date : 2025-06-30 DOI: 10.1016/j.cophys.2025.100847
Arpita Ghosh Mitra
{"title":"Noncoding RNA in cancer: pathogenesis to therapeutic targets","authors":"Arpita Ghosh Mitra","doi":"10.1016/j.cophys.2025.100847","DOIUrl":"10.1016/j.cophys.2025.100847","url":null,"abstract":"<div><div>In the human genome, most transcribed RNA does not translate into protein, yet it plays a crucial role in gene expression regulation. This ‘dark matter of the genome’ is called noncoding RNAs (ncRNAs), which are involved in the pathogenesis of different diseases, viz., cancer. According to the length of nucleotides, ncRNAs are categorised into long ncRNAs (lncRNAs) or small ncRNAs. Recent emerging studies are exploring the massive role of ncRNAs behind pathophysiology and the scope of utilising these huge segments as diagnostic and prognostic indicators, as well as therapeutic targets of cancer. This brief and succinct review will focus on recent publications on the status and major contribution of ncRNAs in cancer, ranging from pathogenesis and diagnosis to prognosis and therapy.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100847"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circadian rhythms in metabolism and mental health: a reciprocal regulatory network with implications for metabolic and neuropsychiatric disorders 代谢和心理健康中的昼夜节律：一个与代谢和神经精神疾病相关的互惠调节网络
IF 2.5
Current Opinion in Physiology Pub Date : 2025-06-02 DOI: 10.1016/j.cophys.2025.100836
Matthew Lloyd , Brooke A Prakash , Lucy Zhao, Guohao Ni, Yining Ru, Sridhar R Vasudevan
{"title":"Circadian rhythms in metabolism and mental health: a reciprocal regulatory network with implications for metabolic and neuropsychiatric disorders","authors":"Matthew Lloyd ,&nbsp;Brooke A Prakash ,&nbsp;Lucy Zhao,&nbsp;Guohao Ni,&nbsp;Yining Ru,&nbsp;Sridhar R Vasudevan","doi":"10.1016/j.cophys.2025.100836","DOIUrl":"10.1016/j.cophys.2025.100836","url":null,"abstract":"<div><div>Circadian rhythms orchestrate metabolism and brain function, aligning internal physiological processes with the 24-hour day–night cycle. Growing evidence highlights a reciprocal relationship between circadian regulation, metabolism, and neurobiological processes. Circadian disruption impairs glucose and lipid homeostasis, alters neurotransmitter and endocrine signalling, and triggers stress response, forming a feedback loop that impacts metabolism and brain function. These disturbances are implicated in many conditions, such as obesity, diabetes, depression, and bipolar disorder. This review examines recent advances in the interplay between circadian regulation, metabolism, and mental health, emphasising shared molecular mechanisms and their role in disease progression. Understanding these connections may ultimately inform therapeutic strategies that integrate circadian-based approaches to improve treatments for metabolic and psychiatric disorders.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100836"},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intersection of sex and circadian biology 性别与昼夜生物学的交叉
IF 2.5
Current Opinion in Physiology Pub Date : 2025-05-30 DOI: 10.1016/j.cophys.2025.100834
Georgios K Paschos, Ronan Lordan, Garret A FitzGerald
{"title":"Intersection of sex and circadian biology","authors":"Georgios K Paschos,&nbsp;Ronan Lordan,&nbsp;Garret A FitzGerald","doi":"10.1016/j.cophys.2025.100834","DOIUrl":"10.1016/j.cophys.2025.100834","url":null,"abstract":"<div><div>The circadian clock aligns behavior and physiology with environmental rhythms, and its disruption has been associated with increased risk of metabolic and neurological diseases. This review examines the emerging trends and mounting evidence demonstrating that there are sex-specific differences in circadian physiology relevant to health. Preclinical and clinical studies indicate that females exhibit greater circadian resilience, robust transcriptional rhythms, and resistance to clock perturbation compared to males. These influences affect susceptibility to metabolic conditions and responses to circadian perturbations like shift work. Notably, sex differences in response to alcohol consumption and cancer chronotherapy have emerged as fields of significant interest. Future research must consider both sexes to refine existing interventions and uncover the complex mechanisms of circadian physiology for more inclusive therapeutic strategies.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100834"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circadian control of cellular constituent turnover and growth 细胞成分周转和生长的昼夜节律控制
IF 2.5
Current Opinion in Physiology Pub Date : 2025-05-27 DOI: 10.1016/j.cophys.2025.100837
Jeffrey J Kelu
{"title":"Circadian control of cellular constituent turnover and growth","authors":"Jeffrey J Kelu","doi":"10.1016/j.cophys.2025.100837","DOIUrl":"10.1016/j.cophys.2025.100837","url":null,"abstract":"<div><div>The circadian clock synchronises biological processes with environmental cues, optimising fitness and energy efficiency. Among these, cell growth regulation is a critical yet underexplored area. While primarily linked to rhythmic cell division, cell growth also arises from the cyclic accumulation of cellular components driving volume expansion. This review highlights advances in understanding how the circadian clock regulates the synthesis and degradation of key cellular constituents, particularly RNAs and proteins, in both homeostatic and growing cells. These processes are essential for maintaining cellular homeostasis and supporting tissue development and regeneration. Further exploration of circadian turnover and its integration with cellular growth pathways could pave the way for chronotherapeutic strategies.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100837"},"PeriodicalIF":2.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SHP2 happens, just sail with it: the role of the protein tyrosine phosphatase SHP2 in autoimmune and autoinflammatory diseases 蛋白酪氨酸磷酸酶SHP2在自身免疫性和自身炎症性疾病中的作用
IF 2.5
Current Opinion in Physiology Pub Date : 2025-05-26 DOI: 10.1016/j.cophys.2025.100833
Samantha Le Sommer , Maria I Kontaridis
{"title":"SHP2 happens, just sail with it: the role of the protein tyrosine phosphatase SHP2 in autoimmune and autoinflammatory diseases","authors":"Samantha Le Sommer ,&nbsp;Maria I Kontaridis","doi":"10.1016/j.cophys.2025.100833","DOIUrl":"10.1016/j.cophys.2025.100833","url":null,"abstract":"<div><div>Autoimmune and autoinflammatory diseases are a diverse group of disorders that stem from aberrant immune responses against self. While autoimmune disorders are characterized by lymphocyte-driven antigen-specific responses, autoinflammatory diseases are driven by chronic activation of the innate immune system. However, to date, both groups of disorders lack clear understanding for their onset and the functional mechanisms conducive to their pathology and have few efficacious, safe, and/or curative treatment options for patients. The SH2 domain–containing protein tyrosine phosphatase (SHP2), the protein encoded by the <em>PTPN11</em> gene, is a nodal enzyme involved in embryogenesis, development, proliferation, differentiation, and survival of cells. Mutations in <em>PTPN11</em> are associated with the development of congenital disorders as well as several types of cancers. Recently, links between autoimmunity and genetic developmental disorders have also revealed a key role for SHP2 activity in autoimmune–autoinflammatory pathophysiology. Its association with these disorders has begun to unravel the molecular mechanisms that contribute to the onset of autoimmunity. In this review, we will discuss the emergent role of SHP2 in autoimmunity and the current known and unknown molecular mechanisms of its regulation in these processes and propose the translational impact it may have as a therapeutic in the near future.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100833"},"PeriodicalIF":2.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From clock genes to exercise: shaping the field of Exercise Chronophysiology 从生物钟基因到运动：塑造运动时间生理学领域
IF 2.5
Current Opinion in Physiology Pub Date : 2025-05-24 DOI: 10.1016/j.cophys.2025.100835
Andrea Ciorciari , Katja A Lamia
{"title":"From clock genes to exercise: shaping the field of Exercise Chronophysiology","authors":"Andrea Ciorciari ,&nbsp;Katja A Lamia","doi":"10.1016/j.cophys.2025.100835","DOIUrl":"10.1016/j.cophys.2025.100835","url":null,"abstract":"<div><div>Circadian rhythms, regulated by central and peripheral clocks, shape physiological processes through clock gene activity and external cues, modulating metabolic pathways, hormonal regulation, and body temperature. By acting on these factors, exercise serves as a powerful zeitgeber, impacting the timing of biological functions. This review highlights insights from molecular to behavioral aspects, examining exercise's role in addressing circadian disruptions, its therapeutic potential for metabolic, psychiatric, and cancer-related conditions, and its applications in enhancing physical performance. Exercise Chronophysiology emerges as a promising integrative approach, offering innovative strategies for promoting health, preventing disease, and optimizing athletic performance.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100835"},"PeriodicalIF":2.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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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