Pathogenesis of Parkinson's disease: oxidative stress, environmental impact factors and inflammatory processes.
Ontology highlight
ABSTRACT:
SUBMITTER: Yuan H
PROVIDER: S-EPMC5550597 | biostudies-other | 2007 Mar
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The current coronavirus pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a serious global health crisis. It is a major concern for individuals living with chronic disorders such as Parkinson's disease (PD). Increasing evidence suggests an involvement of oxidative stress and contribution of NF?B in the development of both COVID-19 and PD. Although, it is early to identify if SARS-CoV-2 led infection enhances PD complications, it is likely that oxidative stress may exacerbate PD progression in COVID-19 affected individuals and/or vice versa. In the current study, we sought to investigate whether NF?B-associated inflammatory pathways following oxidative stress in SARS-CoV-2 and PD patients are correlated. Toward this goal, we have integrated bioinformatics analysis obtained from Basic Local Alignment Search Tool of Protein Database (BLASTP) search for similarities of SARS-CoV-2 proteins against human proteome, literature review, and laboratory data obtained in a human cell model of PD. A Parkinson's like state was created in 6-hydroxydopamine (6OHDA)-induced differentiated dopamine-containing neurons (dDCNs) obtained from an immortalized human neural progenitor cell line derived from the ventral mesencephalon region of the brain (ReNVM). The results indicated that SARS-CoV-2 infection and 6OHDA-induced toxicity triggered stimulation of caspases-2, -3 and -8 via the NF?B pathway resulting in the death of dDCNs. Furthermore, specific inhibitors for NF?B and studied caspases reduced the death of stressed dDCNs. The findings suggest that knowledge of the selective inhibition of caspases and NF?B activation may contribute to the development of potential therapeutic approaches for the treatment of COVID-19 and PD.
| S-EPMC7693814 | biostudies-literature
Project description:Globally, respiratory diseases are major cause of disability and mortality, and more alarmingly, it disproportionately affects developing countries, which is largely attributed to poor quality of air. Tobacco smoke and emissions from combustion of fossil fuel and biomass fuel are the major airborne pollutants affecting human lung health. Oxidative stress is the dominant driving force by which the airborne pollutants exert their toxicity in lungs and cause respiratory diseases. Most airborne pollutants are associated with intrinsic oxidative potential and, additionally, stimulate endogenous production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Elevated ROS and RNS in lungs modulate redox signals and cause irreversible damage to critical biomolecules (lipids, proteins and DNA) and initiate various pathogenic cellular process. This chapter provides an insight into oxidative stress-linked pathogenic cellular process such as lipid peroxidation, inflammation, cell death, mitochondrial dysfunction, endoplasmic reticulum stress, epigenetic changes, profibrotic signals and mucus hypersecretion, which drive the development and progression of lung diseases. Lungs are associated with robust enzymatic and non-enzymatic (GSH, ascorbic acid, uric acid, vitamin E) antioxidant defences. However, sustained production of free radicals due to continuous exposures to airborne pollutants overwhelms lung antioxidant defences and causes oxidative injury. Preclinical studies have demonstrated the critical roles and therapeutic potential of upregulating lung antioxidants for intervention of respiratory diseases; however, so far clinical benefits in antioxidant supplementation trials have been minimal and conflicting. Antioxidants alone may not be effective in treatment of respiratory diseases; however it could be a promising adjunctive therapy.
| S-EPMC7120104 | biostudies-literature
Project description:Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.
| S-EPMC8775426 | biostudies-literature
Project description:Parkinson's disease (PD) is caused by progressive neurodegeneration of dopaminergic (DAergic) neurons with abnormal accumulation of ?-synuclein in substantia nigra (SN). Studies have suggested the potential involvement of dopamine, iron, calcium, mitochondria and neuroinflammation in contributing to overwhelmed oxidative stress and neurodegeneration in PD. Function studies on PD-causative mutations of SNCA, PRKN, PINK1, DJ-1, LRRK2, FBXO7 and ATP13A2 further indicate the role of oxidative stress in the pathogenesis of PD. Therefore, it is reasonable that molecules involved in oxidative stress, such as DJ-1, coenzyme Q10, uric acid, 8-hydroxy-2'-deoxyguanosin, homocysteine, retinoic acid/carotenes, vitamin E, glutathione peroxidase, superoxide dismutase, xanthine oxidase and products of lipid peroxidation, could be candidate biomarkers for PD. Applications of antioxidants to modulate oxidative stress could be a strategy in treating PD. Although a number of antioxidants, such as creatine, vitamin E, coenzyme Q10, pioglitazone, melatonin and desferrioxamine, have been tested in clinical trials, none of them have demonstrated conclusive evidence to ameliorate the neurodegeneration in PD patients. Difficulties in clinical studies may be caused by the long-standing progression of neurodegeneration, lack of biomarkers for premotor stage of PD and inadequate drug delivery across blood-brain barrier. Solutions for these challenges will be warranted for future studies with novel antioxidative treatment in PD patients.
| S-EPMC7402083 | biostudies-literature
Project description:Stress seems to contribute to the neuropathology of Parkinson's disease (PD), possibly by dysregulation of the hypothalamic-pituitary-adrenal axis. Oxidative distress and mitochondrial dysfunction are key factors involved in the pathophysiology of PD and neuronal glucocorticoid-induced toxicity. Animal PD models have been generated to study the effects of hormonal stress, but no in vitro model has yet been developed. Our aim was to examine the impact of corticosterone (CORT) administration on a dopaminergic neuronal cell model of PD induced by the neurotoxin MPP+, as a new combined PD model based on the marker of endocrine response to stress, CORT, and oxidative-mitochondrial damage. We determined the impact of CORT, MPP+ and their co-incubation on reactive oxygen species production (O2-•), oxidative stress cellular markers (advanced-oxidation protein products and total antioxidant status), mitochondrial function (mitochondrial membrane potential and mitochondrial oxygen consumption rate) and neurodegeneration (Fluoro-Jade staining). Accordingly, the administration of MPP+ or CORT individually led to cell damage compared to controls (p < 0.05), as determined by several methods, whereas their co-incubation produced strong cell damage (p < 0.05). The combined model described here could be appropriate for investigating neuropathological hallmarks and for evaluating potential new therapeutic tools for PD patients suffering mild to moderate emotional stress.
| S-EPMC8391158 | biostudies-literature
Project description:Neuroinflammation and oxidative stress play key roles in the pathological development of Parkinson's disease (PD). Nerve growth factor-induced gene B (Nur77) is closely related to dopamine neurotransmission, and its pathogenesis is unclear. This study aims to investigate the role and mechanism of Nur77 in a cell model of Parkinson's disease. Silencing Nur77 with siRNA can aggravate intracellular LDH release, increase the expression of pro-inflammatory genes (such as tumor necrosis factor ?, nuclear factor ?B (p65), monocyte chemotactic protein 1, interleukin-6), and decrease cell survival, decrease expression of nuclear factor E2-related factor(Nrf2), heme oxygenase 1, NADPH quinineoxidoreductase-1. Cytosporone B (Nur77 agonist) has the opposite effect to Nur77 silencing. PDTC (NF-?B inhibitor / antioxidant) can also inhibit pro-inflammatory genes to a similar degree as Cytosporone B. Phosphorylated I?B-? can be inhibited by Cytosporone B, while silencing Nur77 can increase the protein expression level of phosphorylated I?B-?. After silencing I?B-?, both Cytosporone B and siNur77 did not affect pro-inflammatory genes and antioxidant stress. These findings reveal the first evidence that Nur77 exerts anti-inflammatory and antioxidant stress effects by inhibiting I?B-? phosphorylation expression in a Parkinson cell model. Nur77 may be a potential therapeutic target for Parkinson's disease.
| S-EPMC7244064 | biostudies-literature
Project description:Stress-related mucosal disease (SRMD) is a common complication in patients in the intensive care unit (ICU). The aim of the present study was to investigate the possible mechanisms for the pathogenesis of SRMD. In total, 38 patients with SRMD were enrolled from an ICU, as well as 15 healthy volunteers. The disease severity of patients in ICU was evaluated using the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Gastric mucosa with the most severe lesions were biopsied for hematoxylin and eosin staining and then assessed by pathological damage scoring. The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD) and ischemic modified albumin (IMA) were also detected. In addition, claudin-3 and inducible nitric oxide (NO) synthase (iNOS) in the gastric mucosa were assessed by western blotting and immunohistochemistry. The average APACHE II score of the patients with SRMD was significantly higher compared with the controls. Moreover, the levels of MDA (4.74±2.89 nmol/ml) and IMA (93.61±10.78 U/ml) in patients with SRMD were significantly higher compared with the controls (P<0.001), while those of SOD (89.66±12.85 U/ml) in the patients with SRMD were significantly lower compared with the controls (P<0.001). Furthermore, compared with the control, iNOS expression was significantly higher (P=0.034), while the expression of claudin-3 was significantly lower in patients with SRMD (P<0.001). The results indicated that APACHE II score was positively correlated with pathological damage score (r=0.639, P<0.001) and levels of MDA (r=0.743, P<0.001), but negatively correlated with the level of SOD (r=-0.392, P=0.015). In addition, MDA was positively correlated with IMA (r=0.380, P=0.018), but negatively correlated with claudin-3 (r=-0.377, P=0.020). Therefore, it was speculated that oxidative stress may play an important role in the pathogenesis of SRMD, and NO levels and cell membrane permeability are altered during this process.
| S-EPMC7499950 | biostudies-literature
Project description:A protein microarray kit (QAR-INF-1-2, RayBiotech Life Inc., Norcross, GA, USA) was used to detect 10 kinds of inflammatory factors in the CSF and serum (nN=5 per group), including IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, MCP-1, and TNF-α.
2023-04-03 | GSE228521 | GEO
Project description:Graves' disease is a most common cause of hyperthyroidism. It is an autoimmune disease, and autoimmune process induces an inflammatory reaction, and reactive oxygen species (ROSs) are among its products. When balance between oxidants and antioxidants is disturbed, in favour of the oxidants it is termed "oxidative stress" (OS). Increased OS characterizes Graves' disease. It seems that the level of OS is increased in subjects with Graves' ophthalmopathy compared to the other subjects with Graves' disease. Among the other factors, OS is involved in proliferation of orbital fibroblasts. Polymorphism of the 8-oxoG DNA N-glycosylase 1 (hOGG1) involved in repair of the oxidative damaged DNA increases in the risk for developing Grave's disease. Treatment with glucocorticoids reduces levels of OS markers. A recent large clinical trial evaluated effect of selenium on mild Graves' ophthalmopathy. Selenium treatment was associated with an improved quality of life and less eye involvement and slowed the progression of Graves' orbitopathy, compared to placebo.
| S-EPMC3235898 | biostudies-literature
Project description:ObjectiveTo investigate the associations between Parkinson's disease and other degenerative parkinsonian syndromes and environmental factors in five European countries.MethodsA case-control study of 959 prevalent cases of parkinsonism (767 with Parkinson's disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson's Disease Society Brain Bank criteria, and those with drug-induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer-administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job-exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson's disease.ResultsAdjusted logistic regression analyses showed significantly increased odds ratios for Parkinson's disease/parkinsonism with an exposure-response relationship for pesticides (low vs no exposure, odds ratio (OR) = 1.13, 95% CI 0.82 to 1.57, high vs no exposure, OR = 1.41, 95% CI 1.06 to 1.88) and ever knocked unconscious (once vs never, OR = 1.35, 95% CI 1.09 to 1.68, more than once vs never, OR = 2.53, 95% CI 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson's disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% CI 0.42 to 0.60). Analyses confined to subjects with Parkinson's disease gave similar results.ConclusionsThe association of pesticide exposure with Parkinson's disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk.
| S-EPMC2078401 | biostudies-literature