Inflammatory Molecular Mediators and Pathways Involved in Vascular Aging and Stroke: A Comprehensive Review

2021 ◽  
Vol 28 ◽  
Author(s):  
Amro M. Soliman ◽  
Srijit Das ◽  
Pasuk Mahakkanukrauh
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Vascular Diseases ◽  
Vascular Aging ◽  
Inflammatory Conditions ◽  
Age Related ◽  
Cardiovascular Pathologies ◽  
Potential Drug Targets

: There is an increase in the incidence of cardiovascular diseases with aging and it is one of the leading causes of death worldwide. The main cardiovascular pathologies include atherosclerosis, stroke, myocardial infarction, hypertension and stroke. Chronic inflammation is one of the significant contributors to the age-related vascular diseases. Therefore, it is important to understand the molecular mechanisms of the persistent inflammatory conditions occurring in the blood vessels as well as the signaling pathways involved. Herein, we performed an extant search of literature involving PubMed, ISI, WoS and Scopus databases for retrieving all relevant articles with the most recent findings illustrating the potential role of various inflammatory mediators along with their proposed activated pathways in the pathogenesis and progression of vascular aging. We also highlight the major pathways contributing to age-related vascular disorders. The outlined molecular mechanisms, pathways and mediators of vascular aging represent potential drug targets that can be utilized to inhibit and/or slow the pathogenesis and progression of vascular aging.

scholarly journals Environmental Contaminants Acting as Endocrine Disruptors Modulate Atherogenic Processes: New Risk Factors for Cardiovascular Diseases in Women?

2021 ◽  
Author(s):  
Silvia Migliaccio ◽  
Viviana M Bimonte ◽  
Zein Mersini Besharat ◽  
Claudia Sabato ◽  
Clara Crescioli ◽  
...  
Keyword(s):  
Endocrine Disruptors ◽  
Successful Aging ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Vascular Diseases ◽  
Unhealthy Lifestyle ◽  
Age Related ◽  
Increased Risk ◽  
Artery Disease ◽  
Cardio Vascular

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, that could facilitate the development of interventions contributing to “successful aging” and improvement of quality of life. Cardio-vascular diseases (CVD) include pathologies affecting heart or blood vessels, such as hyperten-sion, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations raising the risk of CVD development. Several factors have been claimed to play a role in the alterations observed in muscle and endothelial cells and leading to increased CVD, such as genetic pattern, smoking, unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the last decades attention has been focused on a potential role of several pollutants which disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatic process and CVD progression.

scholarly journals Mefloquine interferes with glycolysis in schistosomula of Schistosoma mansoni via inhibition of enolase

Parasitology ◽  
2012 ◽  
Vol 139 (4) ◽  
pp. 497-505 ◽  
Author(s):  
THERESIA MANNECK ◽  
JENNIFER KEISER ◽  
JOACHIM MÜLLER
Keyword(s):  
Mass Spectrometry ◽  
Schistosoma Mansoni ◽  
Sodium Fluoride ◽  
Drug Targets ◽  
Potential Role ◽  
Glycolytic Enzyme ◽  
Potential Drug ◽  
Crude Extracts ◽  
Potential Drug Targets

SUMMARYThe antimalarial drug mefloquine has promising antischistosomal properties killing haematophagous adult schistosomes as well as schistosomula. The mode of action and involved drug targets of mefloquine in Schistosoma mansoni schistosomula are unknown. In order to identify mefloquine-binding proteins and thus potential drug targets, mefloquine affinity chromatography with S. mansoni schistosomula crude extracts was performed. We found one specific mefloquine-binding protein that was identified by mass spectrometry as the glycolytic enzyme enolase (Q27877). Enolase activity assays were performed on schistosomula crude extracts and on the recombinant enolase Q27877 expressed in Escherichia coli. In schistosomula crude extracts enolase activity was inhibited by mefloquine and by the enolase inhibitor sodium fluoride, while activity of the recombinant enolase was not affected. In contrast to enolase from crude extracts, recombinant Q27877 did not bind to mefloquine-agarose. Using isothermal microcalorimetry, we next investigated the metabolic inhibition of mefloquine and 3 known glycolytic inhibitors in Schistosoma spp., namely sodium fluoride, 3-bromopyruvate and menadione on schistosomula in the presence or absence of glucose. We found that in the presence of glucose, schistosomula were less affected by mefloquine, sodium fluoride and 3-bromopyruvate, whereas glucose had no protective effect when schistosomula had been exposed to menadione. These results suggest a potential role of mefloquine as an inhibitor of glycolysis, at least in stages where other targets like haem degradation are not relevant.

scholarly journals Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence

2021 ◽  
Vol 22 (6) ◽  
pp. 3107
Author(s):  
Noemi Sola-Sevilla ◽  
Ana Ricobaraza ◽  
Ruben Hernandez-Alcoceba ◽  
Maria S. Aymerich ◽  
Rosa M. Tordera ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Potential Role ◽  
Adeno Associated Virus ◽  
Age Related ◽  
Age Dependent ◽  
Molecular Effects ◽  
Samp8 Mice ◽  
The Brain

Sirtuin 2 (SIRT2) has been associated to aging and age-related pathologies. Specifically, an age-dependent accumulation of isoform 3 of SIRT2 in the CNS has been demonstrated; however, no study has addressed the behavioral or molecular consequences that this could have on aging. In the present study, we have designed an adeno-associated virus vector (AAV-CAG-Sirt2.3-eGFP) for the overexpression of SIRT2.3 in the hippocampus of 2 month-old SAMR1 and SAMP8 mice. Our results show that the specific overexpression of this isoform does not induce significant behavioral or molecular effects at short or long term in the control strain. Only a tendency towards a worsening in the performance in acquisition phase of the Morris Water Maze was found in SAMP8 mice, together with a significant increase in the pro-inflammatory cytokine Il-1β. These results suggest that the age-related increase of SIRT2.3 found in the brain is not responsible for induction or prevention of senescence. Nevertheless, in combination with other risk factors, it could contribute to the progression of age-related processes. Understanding the specific role of SIRT2 on aging and the underlying molecular mechanisms is essential to design new and more successful therapies for the treatment of age-related diseases.

DUBs, the regulation of cell identity and disease

2014 ◽  
Vol 465 (1) ◽  
pp. 1-26 ◽  
Author(s):  
Johanna Heideker ◽  
Ingrid E. Wertz
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Cell Identity ◽  
Receptor Signalling ◽  
Future Success ◽  
Potential Drug Targets

The post-translational modification of proteins with ubiquitin represents a complex signalling system that co-ordinates essential cellular functions, including proteolysis, DNA repair, receptor signalling and cell communication. DUBs (deubiquitinases), the enzymes that disassemble ubiquitin chains and remove ubiquitin from proteins, are central to this system. Reflecting the complexity and versatility of ubiquitin signalling, DUB activity is controlled in multiple ways. Although several lines of evidence indicate that aberrant DUB function may promote human disease, the underlying molecular mechanisms are often unclear. Notwithstanding, considerable interest in DUBs as potential drug targets has emerged over the past years. The future success of DUB-based therapy development will require connecting the basic science of DUB function and enzymology with drug discovery. In the present review, we discuss new insights into DUB activity regulation and their links to disease, focusing on the role of DUBs as regulators of cell identity and differentiation, and discuss their potential as emerging drug targets.

scholarly journals Environmental Contaminants Acting as Endocrine Disruptors Modulate Atherogenic Processes: New Risk Factors for Cardiovascular Diseases in Women?

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 44
Author(s):  
Silvia Migliaccio ◽  
Viviana M. Bimonte ◽  
Zein Mersini Besharat ◽  
Claudia Sabato ◽  
Andrea Lenzi ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Endocrine Disruptors ◽  
Successful Aging ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Unhealthy Lifestyle ◽  
Age Related ◽  
Increased Risk ◽  
Artery Disease

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, which could facilitate the development of interventions contributing to “successful aging” and improving quality of life. Cardiovascular diseases (CVD) include pathologies affecting the heart or blood vessels, such as hypertension, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations that raise the risk of CVD development. Several factors have been reported to play a role in the alterations observed in muscle and endothelial cells and that lead to increased CVD, such as genetic pattern, smoking and unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the past decades attention has been focused on a potential role of several pollutants that disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatous degeneration process and CVD progression.

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

scholarly journals Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammed M. Almutairi ◽  
Farzane Sivandzade ◽  
Thamer H. Albekairi ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Cell Infiltration ◽  
Cellular Mechanisms ◽  
Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

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