Hypertension disrupts cerebral blood flow,leading to endothelial dysfunction,breakdown of the blood-brain barrier(BBB),and inflammatory cell infiltration.This cascade triggers glial cell activation,increases oxidative...Hypertension disrupts cerebral blood flow,leading to endothelial dysfunction,breakdown of the blood-brain barrier(BBB),and inflammatory cell infiltration.This cascade triggers glial cell activation,increases oxidative stress,and causes pro-inflammatory cytokine release,creating a neurotoxic environment.In this context,we explore the intricate connection between hypertension,neuroinflammation,and neurodegeneration,as well as how hypertension interacts with other metabolic disorders,such as obesity and diabetes,to further worsen neuroinflammation.Additionally,we discuss the role of the reninangiotensin-aldosterone system,the impact of the microbiome,and the potential contribution of chronic infections in exacerbating neuroinflammation.It is essential to emphasize the potential of nanotechnology to transform therapeutic approaches.Nanoparticle-based drug delivery systems can enhance the bioavailability and selectivity of antihypertensive drugs,antioxidants,and neuroprotective compounds,enabling targeted delivery across the BBB.By combining effective blood pressure management with nanotechnology-enabled therapies that modulate inflammation,oxidative stress,and protein aggregation,we can explore new avenues for preventing and treating hypertension and metabolic disorder-associated neurodegenerative conditions.Ultimately,hypertension significantly contributes to neuroinflammation and neurodegeneration by promoting neuronal cell death,primarily through impaired cerebral blood flow and disruption of the BBB.The interaction of hypertension with metabolic disorders exacerbates these effects.However,advancements in our understanding and new technologies reveal promising nanopharmacological approaches for targeted drug delivery to the brain,thereby improving treatment outcomes,enhancing adherence,and reducing side effects.展开更多
The interplay between mitochondria,epigenetics,and the microbiota is intricately linked to both health and disease.Within our cells,a complex molecular dance occurs,where these components intertwine in a mesmerizing b...The interplay between mitochondria,epigenetics,and the microbiota is intricately linked to both health and disease.Within our cells,a complex molecular dance occurs,where these components intertwine in a mesmerizing ballet that plays a decisive role in our health.Mitochondria,beyond being energy powerhouses,modulate nuclear gene expression through messengers like reactive oxidative stress(ROS)and calcium.Epigenetics,acting as the molecular conductor,regulates the expression of both nuclear and mitochondrial genes through modifications like DNA methylation.The intestinal microbiota itself produces short-chain fatty acids(SCFAs)that influence mitochondrial activity.SCFA-induced epigenetic modifications,like histone acetylation,impact mitochondrial function which may lead to disease.Mitochondrial dysfunction generates retrograde signals that alter nuclear gene expression,as evidenced by increased histone H3 lysine 27 acetylation(H3K27ac)in genes essential for neuronal differentiation and mitochondrial reprogramming.Alterations in the mitochondrial-nuclear-microbiota axis are associated with diseases including diabetes,neurodegeneration,and cancer.Modulating the intestinal microbiota with probiotics or prebiotics can restore balance while intervening in mitochondrial pathways,which can be a therapeutic strategy.Additionally,using epigenetic agents like histone deacetylase(HDAC)inhibitors can reprogram gene expression and improve mitochondrial function.Finally,the present review aims to explore the central interplay between mitochondria,epigenetics modifications,and microbiota in a complex and dynamic molecular context that plays a fundamental role in human health.Specifically,it will examine the impact of microbiome components and metabolites generated from normobiosis and dysbiosis on mitochondria and epigenetic modifications across different diseases and metabolic conditions.This integrated understanding of the molecular players and their interactions provides a deeper perspective on how to promote health and potentially combat disease.展开更多
Mitochondrial dysfunction is a key driver of cardiovascular disease(CVD)in metabolic syndrome and diabetes.This dysfunction promotes the production of reactive oxygen species(ROS),which cause oxidative stress and infl...Mitochondrial dysfunction is a key driver of cardiovascular disease(CVD)in metabolic syndrome and diabetes.This dysfunction promotes the production of reactive oxygen species(ROS),which cause oxidative stress and inflammation.Angiotensin II,the main mediator of the renin-angiotensin-aldosterone system,also contributes to CVD by promoting ROS production.Reduced activity of sirtuins(SIRTs),a family of proteins that regulate cellular metabolism,also worsens oxidative stress.Reduction of energy production by mitochondria is a common feature of all metabolic disorders.High SIRT levels and 5’adenosine monophosphate-activated protein kinase signaling stimulate hypoxia-inducible factor 1 beta,which promotes ketosis.Ketosis,in turn,increases autophagy and mitophagy,processes that clear cells of debris and protect against damage.Sodiumglucose cotransporter-2 inhibitors(SGLT2i),a class of drugs used to treat type 2 diabetes,have a beneficial effect on these mechanisms.Randomized clinical trials have shown that SGLT2i improves cardiac function and reduces the rate of cardiovascular and renal events.SGLT2i also increase mitochondrial efficiency,reduce oxidative stress and inflammation,and strengthen tissues.These findings suggest that SGLT2i hold great potential for the treatment of CVD.Furthermore,they are proposed as anti-aging drugs;however,rigorous research is needed to validate these preliminary findings.展开更多
基金Supported by Agencia Nacional de Promoción de la Investigación,el Desarrollo Tecnológico y la Innovación,No.PICT 2020 Serie A 4000.
文摘Hypertension disrupts cerebral blood flow,leading to endothelial dysfunction,breakdown of the blood-brain barrier(BBB),and inflammatory cell infiltration.This cascade triggers glial cell activation,increases oxidative stress,and causes pro-inflammatory cytokine release,creating a neurotoxic environment.In this context,we explore the intricate connection between hypertension,neuroinflammation,and neurodegeneration,as well as how hypertension interacts with other metabolic disorders,such as obesity and diabetes,to further worsen neuroinflammation.Additionally,we discuss the role of the reninangiotensin-aldosterone system,the impact of the microbiome,and the potential contribution of chronic infections in exacerbating neuroinflammation.It is essential to emphasize the potential of nanotechnology to transform therapeutic approaches.Nanoparticle-based drug delivery systems can enhance the bioavailability and selectivity of antihypertensive drugs,antioxidants,and neuroprotective compounds,enabling targeted delivery across the BBB.By combining effective blood pressure management with nanotechnology-enabled therapies that modulate inflammation,oxidative stress,and protein aggregation,we can explore new avenues for preventing and treating hypertension and metabolic disorder-associated neurodegenerative conditions.Ultimately,hypertension significantly contributes to neuroinflammation and neurodegeneration by promoting neuronal cell death,primarily through impaired cerebral blood flow and disruption of the BBB.The interaction of hypertension with metabolic disorders exacerbates these effects.However,advancements in our understanding and new technologies reveal promising nanopharmacological approaches for targeted drug delivery to the brain,thereby improving treatment outcomes,enhancing adherence,and reducing side effects.
文摘The interplay between mitochondria,epigenetics,and the microbiota is intricately linked to both health and disease.Within our cells,a complex molecular dance occurs,where these components intertwine in a mesmerizing ballet that plays a decisive role in our health.Mitochondria,beyond being energy powerhouses,modulate nuclear gene expression through messengers like reactive oxidative stress(ROS)and calcium.Epigenetics,acting as the molecular conductor,regulates the expression of both nuclear and mitochondrial genes through modifications like DNA methylation.The intestinal microbiota itself produces short-chain fatty acids(SCFAs)that influence mitochondrial activity.SCFA-induced epigenetic modifications,like histone acetylation,impact mitochondrial function which may lead to disease.Mitochondrial dysfunction generates retrograde signals that alter nuclear gene expression,as evidenced by increased histone H3 lysine 27 acetylation(H3K27ac)in genes essential for neuronal differentiation and mitochondrial reprogramming.Alterations in the mitochondrial-nuclear-microbiota axis are associated with diseases including diabetes,neurodegeneration,and cancer.Modulating the intestinal microbiota with probiotics or prebiotics can restore balance while intervening in mitochondrial pathways,which can be a therapeutic strategy.Additionally,using epigenetic agents like histone deacetylase(HDAC)inhibitors can reprogram gene expression and improve mitochondrial function.Finally,the present review aims to explore the central interplay between mitochondria,epigenetics modifications,and microbiota in a complex and dynamic molecular context that plays a fundamental role in human health.Specifically,it will examine the impact of microbiome components and metabolites generated from normobiosis and dysbiosis on mitochondria and epigenetic modifications across different diseases and metabolic conditions.This integrated understanding of the molecular players and their interactions provides a deeper perspective on how to promote health and potentially combat disease.
文摘Mitochondrial dysfunction is a key driver of cardiovascular disease(CVD)in metabolic syndrome and diabetes.This dysfunction promotes the production of reactive oxygen species(ROS),which cause oxidative stress and inflammation.Angiotensin II,the main mediator of the renin-angiotensin-aldosterone system,also contributes to CVD by promoting ROS production.Reduced activity of sirtuins(SIRTs),a family of proteins that regulate cellular metabolism,also worsens oxidative stress.Reduction of energy production by mitochondria is a common feature of all metabolic disorders.High SIRT levels and 5’adenosine monophosphate-activated protein kinase signaling stimulate hypoxia-inducible factor 1 beta,which promotes ketosis.Ketosis,in turn,increases autophagy and mitophagy,processes that clear cells of debris and protect against damage.Sodiumglucose cotransporter-2 inhibitors(SGLT2i),a class of drugs used to treat type 2 diabetes,have a beneficial effect on these mechanisms.Randomized clinical trials have shown that SGLT2i improves cardiac function and reduces the rate of cardiovascular and renal events.SGLT2i also increase mitochondrial efficiency,reduce oxidative stress and inflammation,and strengthen tissues.These findings suggest that SGLT2i hold great potential for the treatment of CVD.Furthermore,they are proposed as anti-aging drugs;however,rigorous research is needed to validate these preliminary findings.
