miR-124 ameliorates dopaminergic neurons loss, reduces oxidative stress via targeting Axin1 and activating Wnt/β-catenin signaling in Parkinson's disease mice

2021 ◽  
pp. 104588
Author(s):  
Fubo Zhang ◽  
Yufang Yao ◽  
Na Miao ◽  
Nan Wang ◽  
Xin Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons

Oxidative Stress to Dopaminergic Neurons as Models of Parkinson's Disease

2004 ◽  
Vol 1018 (1) ◽  
pp. 533-540 ◽  
Author(s):  
G GILLE ◽  
S-T HUNG ◽  
H REICHMANN ◽  
W-D RAUSCH
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons

scholarly journals Blood Exosomes Have Neuroprotective Effects in a Mouse Model of Parkinson’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ting Sun ◽  
Zhe-Xu Ding ◽  
Xin Luo ◽  
Qing-Shan Liu ◽  
Yong Cheng
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Amino Acid ◽  
Dopaminergic Neurons ◽  
Motor Coordination ◽  
Oxidized Lipids ◽  
Metabolomic Analysis ◽  
Neuroprotective Effects ◽  
And Control

Parkinson’s disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.

scholarly journals Demonstration of brain region-specific neuronal vulnerability in human iPSC-based model of familial Parkinson’s disease

2020 ◽  
Vol 29 (7) ◽  
pp. 1180-1191
Author(s):  
Razvan-Marius Brazdis ◽  
Julian E Alecu ◽  
Daniel Marsch ◽  
Annika Dahms ◽  
Katrin Simmnacher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Region ◽  
Neuronal Death ◽  
Dopaminergic Neurons ◽  
Control Individual ◽  
Projection Neurons ◽  
Cortical Projection ◽  
Human Ipscs

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder characterized by protein inclusions mostly composed of aggregated forms of α-synuclein (α-Syn) and by the progressive degeneration of midbrain dopaminergic neurons (mDANs), resulting in motor symptoms. While other brain regions also undergo pathologic changes in PD, the relevance of α-Syn aggregation for the preferential loss of mDANs in PD pathology is not completely understood yet. To elucidate the mechanisms of the brain region-specific neuronal vulnerability in PD, we modeled human PD using human-induced pluripotent stem cells (iPSCs) from familial PD cases with a duplication (Dupl) of the α-Syn gene (SNCA) locus. Human iPSCs from PD Dupl patients and a control individual were differentiated into mDANs and cortical projection neurons (CPNs). SNCA dosage increase did not influence the differentiation efficiency of mDANs and CPNs. However, elevated α-Syn pathology, as revealed by enhanced α-Syn insolubility and phosphorylation, was determined in PD-derived mDANs compared with PD CPNs. PD-derived mDANs exhibited higher levels of reactive oxygen species and protein nitration levels compared with CPNs, which might underlie elevated α-Syn pathology observed in mDANs. Finally, increased neuronal death was observed in PD-derived mDANs compared to PD CPNs and to control mDANs and CPNs. Our results reveal, for the first time, a higher α-Syn pathology, oxidative stress level, and neuronal death rate in human PD mDANs compared with PD CPNs from the same patient. The finding implies the contribution of pathogenic α-Syn, probably induced by oxidative stress, to selective vulnerability of substantia nigra dopaminergic neurons in human PD.

scholarly journals Dysfunction of mitochondria as the basis of Parkinson’s disease

2018 ◽  
Vol 6 (4) ◽  
pp. 174-181
Author(s):  
Małgorzata Popis
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Dopaminergic Neurons ◽  
Genetic Factors ◽  
Lewy Bodies ◽  
Main Ingredient ◽  
Mitochondrial Dynamic ◽  
Factors Affecting

AbstractParkinson's disease is the second most common neurodegenerative disease, affecting about 0,15-0,3% of the world's population. Its characteristic feature is a loss of dopaminergic neurons in the substantia nigra. PD leads to dopamine deficiency and formation of intracellular inclusions called Lewy bodies, whose main ingredient is α-synuclein. Other types of nervous system cells are also affected by changes associated with that disease. The underlying molecular pathogenesis involves multiple pathways and mechanisms: mitochondrial function, oxidative stress, genetic factors, α-synuclein proteostasis, mitochondrial dynamic impairment, and disorders of the mitophagy process. This review summarizes the factors affecting the functioning of the mitochondria and their connection to the development of Parkinson's disease.

scholarly journals Lipid-Mediated Oxidative Stress and Inflammation in the Pathogenesis of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Tahira Farooqui ◽  
Akhlaq A. Farooqui
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Platelet Activating Factor ◽  
Lipid Mediators ◽  
Unknown Etiology ◽  
Oxygen Species ◽  
Progressive Loss ◽  
Progressive Neurodegeneration

Parkinson's disease (PD) is a neurodegenerative movement disorder of unknown etiology. PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, depletion of dopamine in the striatum, abnormal mitochondrial and proteasomal functions, and accumulation ofα-synuclein that may be closely associated with pathological and clinical abnormalities. Increasing evidence indicates that both oxidative stress and inflammation may play a fundamental role in the pathogenesis of PD. Oxidative stress is characterized by increase in reactive oxygen species (ROS) and depletion of glutathione. Lipid mediators for oxidative stress include 4-hydroxynonenal, isoprostanes, isofurans, isoketals, neuroprostanes, and neurofurans. Neuroinflammation is characterized by activated microglial cells that generate proinflammatory cytokines, such as TNF-αand IL-1β. Proinflammatory lipid mediators include prostaglandins and platelet activating factor, together with cytokines may play a prominent role in mediating the progressive neurodegeneration in PD.

scholarly journals Artemisinin Attenuated Oxidative Stress and Apoptosis by Inhibiting Autophagy in MPP+-treated SH-SY5Y Cell 

2020 ◽  
Author(s):  
Junqiang Yan ◽  
Hongxia Ma ◽  
Xiaoyi Lai ◽  
Jiannan Wu ◽  
Anran Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Artemisia Annua ◽  
Cell Model ◽  
Neuroprotective Effect ◽  
Critical Role ◽  
Neuroprotective Effects ◽  
Pre Treatment

Abstract Background Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's. The drugs currently used to treat PD cannot inhibit the development of PD, and long-term use produces severe drug resistance and adverse reaction. Artemisinin (ART) is an active ingredient of Artemisia annua and has a neuroprotective effect, but the mechanism is still unclear. This study was designed to investigate the neuroprotective effect of ART in MPP+-treated SH-SY5Y cells. Results There was no significant cytotoxicity when the ART concentration was under. 40μM. The 20μM ART for 24h could increase the cell viability by reducing oxidative stress and cell apoptosis in MPP+-treated SH-SY5Y cell. In addition, immunoblot and immunofluorescence results showed that MPP+ treatment increased the expression of Beclin1, LC3II/LC3I and decreased the expression of P62, while ART can reverse the changes caused by MPP+. Discussion More and more researches reported that ART and its derivates have neuroprotective effects through anti-oxidant and anti-apoptosis. we found that pre-treated cells with 20μM ART for 4h could significantly increase the viability in Parkinson's disease cell model. The oxidative stress and apoptosis were the main reason for the degeneration of dopaminergic neurons, while artemisinin can attenuate oxidative stress and apoptosis in MPP+-lesioned dopaminergic neurons. The levels of autophagy proteins LC3II/I, Beclin1 and P62 also showed that MPP+ increased the autophagy level, and pre-treatment with ART decreased the autophagy level, which may be the pathological mechanism for artemisinin to reduce oxidative stress damage and apoptosis. Conclusions These results indicate that ART exerts a positive effect on MPP+-treated SH-SY5Y cells in terms of anti-oxidative stress and anti-apoptosis. These effects may be related to autophagy. These findings contribute to a better understanding of the critical role of ART in PD treatment.

scholarly journals MYRICETIN ISOLATED FROM TURBINARIA ORNATA AMELIORATES ROTENONE INDUCED PARKINSONISM IN DROSOPHILA MELANOGASTER

2017 ◽  
Vol 9 (10) ◽  
pp. 39
Author(s):  
Vijayraja Dhanraj ◽  
Tamilarasan Manivasagam ◽  
Jeyaprakash Karuppaiah
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Dopaminergic Neurons ◽  
Fruit Flies ◽  
Neuroprotective Activity ◽  
Dopamine Level ◽  
Enzymatic Antioxidants ◽  
Turbinaria Ornata

Objective: Parkinson’s disease (PD) is a neurodegenerative disorder which affects the elderly population. Free radicals overproduction, oxidative stress, apoptosis, inflammation and abnormalities in mitochondria are critical mediators of the neuronal degeneration. In the present study neuroprotective activity of myricetin, a flavonoid isolated from brown seaweed Turbinaria ornata have been investigated in rotenone induced experimental PD models of Drosophila melanogaster.Methods: Male fruit flies (Drosophila melanogaster) were fed with an effective dose of 0.1% myricetin three hours before to the treatment with 500 µM of Rotenone (LD 50) for seven days and on 8th day through behavioral analysis the neuroprotective effect of myricetin was investigated for motor coordination in fruit flies. Lipid peroxidation was analyzed by estimating the levels of TBARS. Oxidative stress was determined by estimating the activities of enzymatic antioxidants superoxide dismutase, catalase, and glutathione peroxidase along with the level of reduced glutathione. Dopamine level was estimated in HPLC column detected at 280 nm with UV detectors and degree of apoptosis was studied apoptotic marker Bcl-2, Bax, caspases-3 and 9, cytochrome c and β-actin expressions in the whole body homogenate of fruit flies of experimental groups homogenized in 500μL of 0.1 M phosphate buffers (ice cold, pH, 7.4) containing 1 mmol EDTA.Results: Myricetin maintains the positive behavioral patterns against motor impairments due to the rotenone toxicity, it creates a balance in oxidant and antioxidant status, reduces the oxidative stress and inhibits apoptosis to retard neurodegeneration and maintains the dopamine level with a significant (p<0.05) difference compared to the rotenone treated group.Conclusion: The flavonoid myricetin by reducing the oxidative stress, maintaining the enzymatic antioxidants status and by inhibiting apoptosis prevents the degeneration of dopaminergic neurons. The dopaminergic neurons prevention reduces the depletion of dopamine and thereby promotes the muscular coordination and psychological well being of fruit flies of experimental group. Further in depth molecular level studies are in need to explore the preventive mechanisms of myricetin in Parkinson’s disease.

scholarly journals Protective Mechanisms of Flavonoids in Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Kasthuri Bai Magalingam ◽  
Ammu Kutty Radhakrishnan ◽  
Nagaraja Haleagrahara
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Movement Disorder ◽  
Dopaminergic Neurons ◽  
Target Therapy ◽  
Cellular Damage ◽  
Substantia Nigra Pars Compacta ◽  
Protective Mechanisms

Parkinson’s disease is a chronic, debilitating neurodegenerative movement disorder characterized by progressive degeneration of dopaminergic neurons in thesubstantia nigra pars compactaregion in human midbrain. To date, oxidative stress is the well accepted concept in the etiology and progression of Parkinson’s disease. Hence, the therapeutic agent is targeted against suppressing and alleviating the oxidative stress-induced cellular damage. Within the past decades, an explosion of research discoveries has reported on the protective mechanisms of flavonoids, which are plant-based polyphenols, in the treatment of neurodegenerative disease using bothin vitroandin vivomodels. In this paper, we have reviewed the literature on the neuroprotective mechanisms of flavonoids in protecting the dopaminergic neurons hence reducing the symptoms of this movement disorder. The mechanism reviewed includes effect of flavonoids in activation of endogenous antioxidant enzymes, suppressing the lipid peroxidation, inhibition of inflammatory mediators, flavonoids as a mitochondrial target therapy, and modulation of gene expression in neuronal cells.

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