Search results for "STRESS"
showing 10 items of 6278 documents
Protein misfolding, amyotrophic lateral sclerosis and guanabenz: Protocol for a phase II RCT with futility design (ProMISe trial)
2017
IntroductionRecent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug. A pharmacological action recently discovered is its ability to modulate the synthesis of proteins by the activation of translational factors preventing misfolded protein accumula…
A free radical theory of frailty.
2018
The free radical theory of ageing provided an intellectual framework for many laboratories working on ageing. However, experimental and clinical evidence showing that high doses of antioxidants do not have an effect on ageing or on age-associated diseases, cast doubts on the validity of this theory. Data from our own laboratory show that oxidative damage does not correlate with age, especially in the geriatric population, but rather with the frailty state. This has led us to postulate the free radical theory of frailty that proposes that oxidative damage is associated with frailty, but not with chronological age itself. Superoxide dismutase deficient mice are more frail than controls. But m…
Sympathetic, metabolic adaptations, and oxidative stress in autism spectrum disorders: How far from physiology?
2018
Autism spectrum disorders (ASD) is a complex and multifaceted neurobehavioral syndrome with no specific cause still identified, despite the worldwide increasing (prevalence for 1,000 children from 6.7 to 14.6, between 2000 and 2012). Many biological and instrumental markers have been suggested as potential predictive factors for the precocious diagnosis during infancy and/or pediatric age. Many studies reported structural and functional abnormalities in the autonomic system in subjects with ASD. Sleep problems in ASD are a prominent feature, having an impact on the social interaction of the patient. Considering the role of orexins (A and B) in wake-sleep circadian rhythm, we could speculate…
Two-Week Aflibercept or Erlotinib Administration Does Not Induce Changes in Intestinal Morphology in Male Sprague–Dawley Rats But Aflibercept Affects…
2019
Gastrointestinal toxicity is a frequently observed adverse event during cancer treatment with traditional chemotherapeutics. Currently, traditional chemotherapeutics are often combined with targeted biologic agents. These biologics, however, possess a distinct toxicity profile, and they may also exacerbate the adverse effects of traditional chemotherapeutics. In this study, we aimed to characterize the gastrointestinal and metabolic changes after a 2-week treatment period with aflibercept, an antiangiogenic VEGFR decoy, and with erlotinib, a tyrosine-kinase inhibitor. Male rats were treated either with aflibercept or erlotinib for 2 weeks. During the 2-week treatment period, the animals in …
αB-crystallin response to a pro-oxidant non-cytotoxic environment in murine cardiac cells: An "in vitro" and "in vivo" study.
2020
The αB-crystallin (HSPB5) protein is modulated in response to a wide variety of stressors generated by multiple physio-pathological conditions, sustained by reactive oxygen species (ROS) production. In cardiac muscle tissue, this protein regulates various cellular processes, such as protein degradation, apoptosis and the stabilization of cytoskeletal elements. In this work, we studied the role of HSPB5 expression, activation and localization in HL-1 murine cardiomyocytes exposed to pro-oxidant and non-cytotoxic H2O2 concentration, as well as in cardiac tissue isolated from mice following an acute, non-damaging endurance exercise. Our results demonstrated that HSPB5 is the most abundant HSP …
Increased basal antioxidant levels in RCAN1 - deficient mice lowers oxidative injury after acute paraquat insult.
2020
RCAN1 is an inhibitor of the phosphatase calcineurin, which is involved in the regulation of oxidative stress and apoptosis, among other important cell processes. Here we have used RCAN1 deficient mice (RCAN1-/-) to elucidate its role after an acute oxidative insult such as paraquat injection. We have observed that RCAN1-/- mice show less oxidative damage than wildtype (WT) mice after treatment. Under basal conditions, RCAN1-/- animals express more calcineurin, heme oxygenase-1, Nrf2, and catalase compared to WT mice (controls). This may explain the less severe effect of paraquat treatment on RCAN1-/- mice compared to WT. We showed that oxidative stress is involved in the early stages of ap…
Enhanced activity of glycolytic enzymes in Drosophila and human cell models of Parkinson's disease based on DJ-1 deficiency
2020
ABSTRACTParkinson’s disease (PD) is a neurodenerative debilitating disorder characterized by progressive disturbances in motor, autonomic and psychiatric functions. The pathological hallmark of PD is the loss of dopaminergic neurons in the substantia nigra pars compacta, which causes striatal dopamine deficiency. Although most PD cases are sporadic (iPD), approximately 5-10% of all patients suffer from monogenic PD forms caused by highly penetrant rare mutations segregating with the disease in families (fPD). One of the genes linked to monogenic PD is DJ-1. Mutations in DJ-1 cause autosomal recessive early-onset forms of fPD; however, it has been shown that an over-oxidized and inactive for…
Identification of potential therapeutic compounds for Parkinson's disease using Drosophila and human cell models.
2017
Abstract Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. It is caused by a loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrease in dopamine levels in the striatum and thus producing movement impairment. Major physiological causes of neurodegeneration in PD are oxidative stress (OS) and mitochondrial dysfunction; these pathophysiological changes can be caused by both genetic and environmental factors. Although most PD cases are sporadic, it has been shown that 5–10% of them are familial forms caused by mutations in certain genes. One of these genes is the DJ-1 oncogene, which is involved in an early…
Reductive Stress: A New Concept in Alzheimer's Disease
2015
Reactive oxygen species play a physiological role in cell signaling and also a pathological role in diseases, when antioxidant defenses are overwhelmed causing oxidative stress. However, in this review we will focus on reductive stress that may be defined as a pathophysiological situation in which the cell becomes more reduced than in the normal, resting state. This may occur in hypoxia and also in several diseases in which a small but persistent generation of oxidants results in a hormetic overexpression of antioxidant enzymes that leads to a reduction in cell compartments. This is the case of Alzheimer's disease. Individuals at high risk of Alzheimer's (because they carry the ApoE4 allele…
Potential Influence of Helminth Molecules on COVID-19 Pathology
2020
In recent months, the parasitology research community has been tasked with investigation of the influence of parasite coinfection on coronavirus disease 2019 (COVID-19) outcomes. Herein, we share our approach to analyze the effect of the trematode Fasciola hepatica as a modulator of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of COVID-19 pathology.