Pub Date : 2025-10-10DOI: 10.1016/j.cophys.2025.100864
Cheng-Wei Lim , Hafizah Abdul Hamid , King Hwa Ling , Pike See Cheah
Down syndrome (DS) individuals experience chronic and widespread oxidative stress across all organs throughout their lives. While the cause of oxidative stress in DS may be difficult to pinpoint, the myriad perturbations investigated to date share commonalities in terms of their mechanisms. Recent studies highlight five main mechanisms of oxidative stress in DS, namely increased production of reactive oxygen species (ROS), decreased antioxidant defense, impaired mitochondrial biology, defective cellular clearance, and altered metabolism. These mechanisms interact with one another to bring about the overproduction of ROS or a reduction in their clearance. This review attempts to summarize the latest perspective and findings regarding these five mechanisms with emerging evidence within the past five years (2020 to 2025).
{"title":"Oxidative stress in Down syndrome: unraveling the intertwined pathways for novel target identification","authors":"Cheng-Wei Lim , Hafizah Abdul Hamid , King Hwa Ling , Pike See Cheah","doi":"10.1016/j.cophys.2025.100864","DOIUrl":"10.1016/j.cophys.2025.100864","url":null,"abstract":"<div><div>Down syndrome (DS) individuals experience chronic and widespread oxidative stress across all organs throughout their lives. While the cause of oxidative stress in DS may be difficult to pinpoint, the myriad perturbations investigated to date share commonalities in terms of their mechanisms. Recent studies highlight five main mechanisms of oxidative stress in DS, namely increased production of reactive oxygen species (ROS), decreased antioxidant defense, impaired mitochondrial biology, defective cellular clearance, and altered metabolism. These mechanisms interact with one another to bring about the overproduction of ROS or a reduction in their clearance. This review attempts to summarize the latest perspective and findings regarding these five mechanisms with emerging evidence within the past five years (2020 to 2025).</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100864"},"PeriodicalIF":1.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363064","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}
Pub Date : 2025-10-10DOI: 10.1016/j.cophys.2025.100867
Khaja Shameem Mohammed Abdul , Inca Stienhans , Shaira Gail Santos , Hollis Rausch , Nicole H Purcell
In recent years, pleckstrin homology domain leucine-rich repeat protein phosphatase-1 (PHLPP1) and 2 (PHLPP2) have emerged as key players in regulating various survival signaling pathways, including Akt, and contribute towards cardiovascular disease development. This review highlights the diverse mechanisms regulating PHLPP1/2 at transcriptional, translational, and post-translational levels and discusses their role in cardiovascular function and disease. We further explore the therapeutic potential of targeting PHLPP1/2 using small molecule inhibitors, peptide inhibitors, microRNAs, long noncoding RNAs, and natural compounds. While the divergent roles of PHLPP1 and PHLPP2 in maintaining cellular homeostasis and their dysregulation in cancer and other diseases are well documented, their regulation and downstream targets in the heart under normal and pathological states remain unclear. Future studies are warranted to discover the regulatory mechanisms of PHLPP1/2, identify novel cardiac stress-regulated substrate kinases and binding partners, and develop therapies that target these phosphatases independently for clinical translation.
{"title":"Recent advances in PHLPP1 and PHLPP2 research: an update in the heart","authors":"Khaja Shameem Mohammed Abdul , Inca Stienhans , Shaira Gail Santos , Hollis Rausch , Nicole H Purcell","doi":"10.1016/j.cophys.2025.100867","DOIUrl":"10.1016/j.cophys.2025.100867","url":null,"abstract":"<div><div>In recent years, pleckstrin homology domain leucine-rich repeat protein phosphatase-1 (PHLPP1) and 2 (PHLPP2) have emerged as key players in regulating various survival signaling pathways, including Akt, and contribute towards cardiovascular disease development. This review highlights the diverse mechanisms regulating PHLPP1/2 at transcriptional, translational, and post-translational levels and discusses their role in cardiovascular function and disease. We further explore the therapeutic potential of targeting PHLPP1/2 using small molecule inhibitors, peptide inhibitors, microRNAs, long noncoding RNAs, and natural compounds. While the divergent roles of PHLPP1 and PHLPP2 in maintaining cellular homeostasis and their dysregulation in cancer and other diseases are well documented, their regulation and downstream targets in the heart under normal and pathological states remain unclear. Future studies are warranted to discover the regulatory mechanisms of PHLPP1/2, identify novel cardiac stress-regulated substrate kinases and binding partners, and develop therapies that target these phosphatases independently for clinical translation.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100867"},"PeriodicalIF":1.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363063","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}
Pub Date : 2025-10-10DOI: 10.1016/j.cophys.2025.100866
Yimin Li , Yuenuo Luo , Xiaodan Zhao , Shiying Wu , Ping Li
Oxidative stress is one of the important mechanisms leading to oxidative aging. The balance between intracellular oxidants and antioxidants is disrupted, resulting in DNA hydroxylation, protein denaturation, lipid peroxidation, and cell apoptosis, ultimately affecting the survival ability of cells. Probiotics and antioxidants are the main means of combating oxidative stress. In recent years, the limitations of using probiotics or antioxidants alone have become increasingly apparent, and the synergistic effect of probiotics and antioxidants has become a new research hotspot. This review synthesizes the current evidence on the synergistic roles of probiotics and antioxidants in mitigating oxidative stress and delaying aging, with an emphasis on mechanistic insights and translational potential.
{"title":"Probiotics and antioxidants: synergistic mechanisms in reducing oxidative stress and anti-aging applications","authors":"Yimin Li , Yuenuo Luo , Xiaodan Zhao , Shiying Wu , Ping Li","doi":"10.1016/j.cophys.2025.100866","DOIUrl":"10.1016/j.cophys.2025.100866","url":null,"abstract":"<div><div>Oxidative stress is one of the important mechanisms leading to oxidative aging. The balance between intracellular oxidants and antioxidants is disrupted, resulting in DNA hydroxylation, protein denaturation, lipid peroxidation, and cell apoptosis, ultimately affecting the survival ability of cells. Probiotics and antioxidants are the main means of combating oxidative stress. In recent years, the limitations of using probiotics or antioxidants alone have become increasingly apparent, and the synergistic effect of probiotics and antioxidants has become a new research hotspot. This review synthesizes the current evidence on the synergistic roles of probiotics and antioxidants in mitigating oxidative stress and delaying aging, with an emphasis on mechanistic insights and translational potential.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100866"},"PeriodicalIF":1.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417054","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}
Pub Date : 2025-10-10DOI: 10.1016/j.cophys.2025.100868
Setor K Kunutsor , Khushmanjot Kaur , Ashish H Shah
Acute coronary syndrome (ACS) remains a global health challenge, with sex differences in outcomes persisting despite major advances in cardiovascular care. Women continue to experience worse short- and long-term outcomes than men, including higher mortality, complications, and hospital readmissions - particularly among younger women. These disparities reflect biological, psychosocial, and healthcare system factors, including delayed diagnosis and lower access to guideline-based interventions. Evidence from low- and middle-income countries, though limited, suggests similar or greater disparities. Most available data are from observational studies, with randomized trials rarely designed to assess sex-specific effects. Addressing these gaps requires sex-informed research, equitable care delivery, and risk prediction tools tailored by sex to improve ACS outcomes globally.
{"title":"Sex differences in acute coronary syndrome outcomes and prognosis: a decade of progress and persistent disparities (2014–2025)","authors":"Setor K Kunutsor , Khushmanjot Kaur , Ashish H Shah","doi":"10.1016/j.cophys.2025.100868","DOIUrl":"10.1016/j.cophys.2025.100868","url":null,"abstract":"<div><div>Acute coronary syndrome (ACS) remains a global health challenge, with sex differences in outcomes persisting despite major advances in cardiovascular care. Women continue to experience worse short- and long-term outcomes than men, including higher mortality, complications, and hospital readmissions - particularly among younger women. These disparities reflect biological, psychosocial, and healthcare system factors, including delayed diagnosis and lower access to guideline-based interventions. Evidence from low- and middle-income countries, though limited, suggests similar or greater disparities. Most available data are from observational studies, with randomized trials rarely designed to assess sex-specific effects. Addressing these gaps requires sex-informed research, equitable care delivery, and risk prediction tools tailored by sex to improve ACS outcomes globally.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100868"},"PeriodicalIF":1.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417053","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}
Pub Date : 2025-10-10DOI: 10.1016/j.cophys.2025.100869
Jovana Joksimovic Jovic , Nikola Jovic , Maja Muric , Vladimir Jakovljevic
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among women of reproductive age and is increasingly recognized as a cardiometabolic condition. In addition to reproductive abnormalities, PCOS is closely linked to an elevated risk of hypertension, insulin resistance, dyslipidemia, visceral adiposity, and early markers of atherosclerosis. Growing evidence indicates that androgen excess, endothelial dysfunction, and related molecular pathways contribute to adverse cardiovascular remodeling. This review integrates recent clinical and experimental findings connecting PCOS to cardiovascular disease (CVD), with particular emphasis on phenotypic variation, hormonal regulation, and sex-specific mechanisms. A better understanding of these interrelationships is essential to refine risk stratification and guide the development of targeted strategies aimed at preventing CVD in this high-risk female population.
{"title":"Polycystic ovary syndrome and cardiometabolic risk: a perspective on women's heart health","authors":"Jovana Joksimovic Jovic , Nikola Jovic , Maja Muric , Vladimir Jakovljevic","doi":"10.1016/j.cophys.2025.100869","DOIUrl":"10.1016/j.cophys.2025.100869","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among women of reproductive age and is increasingly recognized as a cardiometabolic condition. In addition to reproductive abnormalities, PCOS is closely linked to an elevated risk of hypertension, insulin resistance, dyslipidemia, visceral adiposity, and early markers of atherosclerosis. Growing evidence indicates that androgen excess, endothelial dysfunction, and related molecular pathways contribute to adverse cardiovascular remodeling. This review integrates recent clinical and experimental findings connecting PCOS to cardiovascular disease (CVD), with particular emphasis on phenotypic variation, hormonal regulation, and sex-specific mechanisms. A better understanding of these interrelationships is essential to refine risk stratification and guide the development of targeted strategies aimed at preventing CVD in this high-risk female population.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100869"},"PeriodicalIF":1.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417055","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}
Pub Date : 2025-09-25DOI: 10.1016/j.cophys.2025.100861
Liang Guo , Ying Gao , Yong-Quan Xu
Oxidative stress occurs when the production of oxidant burden exceeds the body’s ability to counteract it. It is a double-edged sword. On one hand, it damages normal cells and increases the risk of health problems. On the other hand, it can damage cancer cells and bacteria, showing potential in chemotherapy and infection treatment. Tea polyphenols (TP) are the main bioactive compounds in tea leaves. They are usually antioxidants, but become pro-oxidants when auto-oxidized or reacted with reduced transition metal ions. In this review, the role of TP as antioxidants in preventing neurodegenerative diseases, skin photoaging, atherosclerosis, and cigarette smoke-induced pulmonary injury, as well as the role of TP as pro-oxidants in anticancer and antibacterial activities are summarized and elucidated.
{"title":"Targeting oxidative stress with tea polyphenols: mechanisms and health benefits","authors":"Liang Guo , Ying Gao , Yong-Quan Xu","doi":"10.1016/j.cophys.2025.100861","DOIUrl":"10.1016/j.cophys.2025.100861","url":null,"abstract":"<div><div>Oxidative stress occurs when the production of oxidant burden exceeds the body’s ability to counteract it. It is a double-edged sword. On one hand, it damages normal cells and increases the risk of health problems. On the other hand, it can damage cancer cells and bacteria, showing potential in chemotherapy and infection treatment. Tea polyphenols (TP) are the main bioactive compounds in tea leaves. They are usually antioxidants, but become pro-oxidants when auto-oxidized or reacted with reduced transition metal ions. In this review, the role of TP as antioxidants in preventing neurodegenerative diseases, skin photoaging, atherosclerosis, and cigarette smoke-induced pulmonary injury, as well as the role of TP as pro-oxidants in anticancer and antibacterial activities are summarized and elucidated.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100861"},"PeriodicalIF":1.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325047","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}
Pub Date : 2025-09-24DOI: 10.1016/j.cophys.2025.100862
Zhijun Meng , Mary K Sewell-Loftin , Vinoy Thomas , Xinliang Ma , Yajing Wang
Small extracellular vesicles (sEVs) have been recognized as critical mediators of intercellular communication, impacting processes such as inflammation, tissue repair, and cardiovascular disease progression. Conventionally, research has focused on the general role of sEVs in mediating the signals among cell–cell communication without specifically considering the underlying molecular regulators.
However, recent insights highlight the emerging importance of Caveolin, a protein integral to the formation of caveolae, in the regulation of EV biogenesis and release, particularly exosomes. This review underscores the novel role of Caveolin in sEV in shaping interorgan communication via sEV-mediated signaling and how it alters the cardiovascular disease development via modulating multiple pathways. These causes of sEVs transport crucial signaling molecules, including small RNAs and proteins, capable of modulating disease progression positively or negatively.
Furthermore, we emphasize novel developments regarding Caveolin-1’s influence on diabetes-related cardiovascular pathologies and metabolic disturbances, specifically insulin secretion, insulin signaling, insulin resistance, oxidative stress, and diabetes-associated complications. By bridging traditional views with recent advancements, this review seeks to provide a comprehensive understanding of Caveolin-1’s potential as a therapeutic target in cardiovascular and metabolic disorders.
{"title":"Caveolin in extracellular vesicles: orchestrating interorgan communication in diabetes-associated cardiovascular disease","authors":"Zhijun Meng , Mary K Sewell-Loftin , Vinoy Thomas , Xinliang Ma , Yajing Wang","doi":"10.1016/j.cophys.2025.100862","DOIUrl":"10.1016/j.cophys.2025.100862","url":null,"abstract":"<div><div>Small extracellular vesicles (sEVs) have been recognized as critical mediators of intercellular communication, impacting processes such as inflammation, tissue repair, and cardiovascular disease progression. Conventionally, research has focused on the general role of sEVs in mediating the signals among cell–cell communication without specifically considering the underlying molecular regulators.</div><div>However, recent insights highlight the emerging importance of Caveolin, a protein integral to the formation of caveolae, in the regulation of EV biogenesis and release, particularly exosomes. This review underscores the novel role of Caveolin in sEV in shaping interorgan communication via sEV-mediated signaling and how it alters the cardiovascular disease development via modulating multiple pathways. These causes of sEVs transport crucial signaling molecules, including small RNAs and proteins, capable of modulating disease progression positively or negatively.</div><div>Furthermore, we emphasize novel developments regarding Caveolin-1’s influence on diabetes-related cardiovascular pathologies and metabolic disturbances, specifically insulin secretion, insulin signaling, insulin resistance, oxidative stress, and diabetes-associated complications. By bridging traditional views with recent advancements, this review seeks to provide a comprehensive understanding of Caveolin-1’s potential as a therapeutic target in cardiovascular and metabolic disorders.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100862"},"PeriodicalIF":1.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325048","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}
Pub Date : 2025-09-20DOI: 10.1016/j.cophys.2025.100863
Dhrubo Ahmad , Taslima Akter Shila , Yuhui Yang , Huilan Tan , Yajing Wang
Impaired cardiac relaxation, or diastolic dysfunction, is a key contributor to heart failure in diabetic patients, making early detection critical for preventing disease progression. This review explores current diagnostic modalities for assessing myocardial relaxation function in diabetes-associated heart failure or heart failure with preserved ejection fraction, including imaging techniques, biomarker analysis, and emerging chip-based technologies. We highlight advancements in echocardiography, cardiac magnetic resonance imaging (MRI), molecular diagnostics, and innovative microfluidic and biosensor-based devices that offer real-time monitoring of myocardial relaxation dynamics. Integrating these diverse modalities holds promise for enhancing early diagnosis and enabling personalized therapeutic approaches to improve patient outcomes.
{"title":"Current diagnostic modalities for detecting myocardial relaxation function in diabetes-associated heart failure or heart failure with preserved ejection fraction","authors":"Dhrubo Ahmad , Taslima Akter Shila , Yuhui Yang , Huilan Tan , Yajing Wang","doi":"10.1016/j.cophys.2025.100863","DOIUrl":"10.1016/j.cophys.2025.100863","url":null,"abstract":"<div><div>Impaired cardiac relaxation, or diastolic dysfunction, is a key contributor to heart failure in diabetic patients, making early detection critical for preventing disease progression. This review explores current diagnostic modalities for assessing myocardial relaxation function in diabetes-associated heart failure or heart failure with preserved ejection fraction, including imaging techniques, biomarker analysis, and emerging chip-based technologies. We highlight advancements in echocardiography, cardiac magnetic resonance imaging (MRI), molecular diagnostics, and innovative microfluidic and biosensor-based devices that offer real-time monitoring of myocardial relaxation dynamics. Integrating these diverse modalities holds promise for enhancing early diagnosis and enabling personalized therapeutic approaches to improve patient outcomes.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100863"},"PeriodicalIF":1.9,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325049","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}
Pub Date : 2025-09-19DOI: 10.1016/j.cophys.2025.100860
Shaira Gail Santos , Khaja Shameem Mohammed Abdul , Nicole H Purcell
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.
{"title":"Protein phosphatases in metabolic dysfunction-associated steatotic liver disease: emerging mechanisms and therapeutic strategies","authors":"Shaira Gail Santos , Khaja Shameem Mohammed Abdul , 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}
Pub Date : 2025-09-12DOI: 10.1016/j.cophys.2025.100859
Carmalena V Cordi , Jennifer M Hurley
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.
{"title":"The link between circadian disruption and Alzheimer’s disease and related dementias: insights from peripheral inflammation","authors":"Carmalena V Cordi , 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}
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