scholarly journals In Vitro Assessment of the Neuroprotective and Antioxidant Properties of New Benzimidazole Derivatives as Potential Drug Candidates for the Treatment of Parkinson’s Disease

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 54
Author(s):  
Anastassova ◽  
Argirova ◽  
Yancheva ◽  
Aluani ◽  
Tzankova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Antioxidant Properties ◽  
Benzimidazole Derivatives ◽  
Potential Drug ◽  
Drug Candidates ◽  
In Vitro Assessment

Oxidative stress is related to the pathogenesis of many neurodegenerative disorders, including [...]

scholarly journals Effect of Curcumin on Protein Damage Induced by Rotenone in Dopaminergic PC12 Cells

2020 ◽  
Vol 21 (8) ◽  
pp. 2761 ◽  
Author(s):  
Sandra Buratta ◽  
Elisabetta Chiaradia ◽  
Alessia Tognoloni ◽  
Angela Gambelunghe ◽  
Consuelo Meschini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Cell Function ◽  
Neurodegenerative Disorder ◽  
Cell Model ◽  
Antioxidant Properties ◽  
Protein Damage ◽  
Substantia Nigra Pars Compacta

Oxidative stress is considered to be a key factor of the pathogenesis of Parkinson’s disease, a multifactorial neurodegenerative disorder characterized by reduced dopaminergic neurons in the substantia nigra pars compacta and accumulated protein aggregates. Rotenone is a worldwide-used pesticide that induces the most common features of Parkinson’s by direct inhibition of the mitochondrial complex I. Rotenone-induced Parkinson’s models, as well as brain tissues from Parkinson’s patients, are characterized by the presence of both lipid peroxidation and protein oxidation markers resulting from the increased level of free radical species. Oxidation introduces several modifications in protein structure, including carbonylation and nitrotyrosine formation, which severely compromise cell function. Due to the link existing between oxidative stress and Parkinson’s disease, antioxidant molecules could represent possible therapeutic tools for this disease. In this study, we evaluated the effect of curcumin, a natural compound known for its antioxidant properties, in dopaminergic PC12 cells treated with rotenone, a cell model of Parkinsonism. Our results demonstrate that the treatment of PC12 cells with rotenone causes severe protein damage, with formation of both carbonylated and nitrotyrosine-derived proteins, whereas curcumin (10 µM) co-exposure exerts protective effects by reducing the levels of oxidized proteins. Curcumin also promotes proteasome activation, abolishing the inhibitory effect exerted by rotenone on this degradative system.

scholarly journals Hesperetin protects SH-SY5Y cells against 6- hydroxydopamine-induced neurotoxicity via activation of NRF2/ARE signaling pathways

2020 ◽  
Vol 19 (6) ◽  
pp. 1197-1201 ◽  
Author(s):  
Jing Li ◽  
Yue Liu ◽  
Li Wang ◽  
Zhaowei Gu ◽  
Zhigang Huan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Viability ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Ldh Release ◽  
6 Hydroxydopamine

Purpose: To investigation the protective effects of hesperetin against 6-hydroxydopamine (6-OHDA)- induced neurotoxicity. Methods: SH-SY5Y cells were incubated with 6-OHDA to create an in vitro model of neurotoxicity. This model was used to test the neuroprotective effects of hesperetin. Cell viability was assessed by MTT and lactate dehydrogenase (LDH) release assays. Flow cytometry and western blot were used to quantify apoptosis. Oxidative stress was evaluated by determining intracellular glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS). Results: In SH-SY5Y cells, treatment with 6-OHDA decreased cell viability and promoted LDH release. However, exogenous hesperetin protected against 6-OHDA-mediated toxicity. Similarly, although incubation with 6-OHDA induced apoptosis and increased cleaved caspase-3 and -9 levels, treatment with hesperetin protected against these effects. Treatment with 6-OHDA also led to significant oxidative stress, as indicated by reduced GSH and SOD levels and increased MDA and ROS levels in SH-SY5Y cells. However, these changes were reversed by pre-treatment with hesperetin. Of interest, hesperetin led to changes in 6-OHDA-induced expression of NRF2, heme oxygenase-1 (HO-1), glutamate-cysteine ligase (GCL) catalytic subunit (GCLC), and GCL modulatory (GCLM). Conclusion: Hesperetin protects against cell toxicity, apoptosis, and oxidative stress via activation of NRF2 pathway in a 6-OHDA-induced model of neurotoxicity. Future studies should investigate the use of hesperetin as a potential therapeutic approach for prevention or management of Parkinson’s disease. Keywords: Hesperetin, 6-OHDA, Neurotoxicity, NRF2, Parkinson’s disease

Molecular simulation studies of Alpha Pinene, an alkene in search for oxidative stress targeted therapeutic paradigms for the treatment of Parkinson’s disease: A computational approach and its in-vitro antioxidant validation

2021 ◽  
Vol 18 ◽  
Author(s):  
Rajnish Srivastava ◽  
Pratim Kumar Choudhury ◽  
Suresh Kumar Dev ◽  
Vaibhav Rathore
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Binding Energy ◽  
Molecular Interaction ◽  
Hypochlorous Acid ◽  
Cell Degeneration ◽  
Mao B ◽  
Alpha Pinene

Aim: The present study was expected to explore the molecular interaction of five oxidative stress (OS) associated target receptors with Alpha-Pinene and its antioxidant validation for the effective treatment of Parkinson’s disease (PD). Background: Oxidative stress (OS) via multitudinous cascades is considered to be the leading attribute to dopaminergic cell degeneration in PD. Furthermore, it is also well-linked to other mechanisms involved in the neurodegeneration process, like dysfunction of mitochondria, neuroinflammation and excitotoxicity due to NO. Objective: The present investigation was to establish a molecular association of OS-associated target receptors with the bioactive compound alpha-pinene and how this molecular interaction empowers the mitigation of PD. Material and Method: Five different molecular targets namely Peroxisome Proliferator-Activated Receptor- Gamma (PPARγ), Liver-X receptor beta (LXR- β), Human Monoamine Oxidase-B (MAO-B), Human Nuclear receptor related-1 protein (Nurr1) and Human Lipoprotein-associated phospholipase A2 (Lp-PLA2) were obtained from RCSB-PDB, which has some leading association in the inhibition of the OS-induced neurodegeneration. Molecular interactions were stuffed by the simulation molecular docking software. Antioxidant activity was validated by in-vitro models as per standardized procedures against 2,2- diphenyl-1- picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline -6-sulfonic acid) (ABTS), Ferric ion (Fe3+), Hydroxyl (•OH), nitric oxide (•NO), Peroxynitrite (ONOO-) and Hypochlorous acid (HOCl). Result: Our results indicated that alpha-pinene can interact with all the five different target receptors at the active binding site of receptors. Alpha-pinene was found to show better interaction with MAO-B, Nurr1 and PPARγ with binding energy of -5.50, -4.52 and -5.25, respectively as compared to the native ligand. Furthermore, the interaction of alpha-pinene with LXR-β and Lp-PLA2 was also significant with binding energy of -5.6 and -5.12, respectively. It also capable of neutralizing all the different free radicals under consideration with significant IC50 values against HOCl and •NO. Conclusion: It might be concluded that alpha-pinene could act as a potential inhibitor and scavenger of OS which could act on the multiple target receptors under consideration.

Evaluation of Levodopa and Carbidopa Antioxidant Activity in Normal Human Lymphocytes In Vitro: Implication for Oxidative Stress in Parkinson’s Disease

2014 ◽  
Vol 27 (2) ◽  
pp. 106-117 ◽  
Author(s):  
Monica Colamartino ◽  
Massimo Santoro ◽  
Guglielmo Duranti ◽  
Stefania Sabatini ◽  
Roberta Ceci ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Antioxidant Activity ◽  
Parkinson's Disease ◽  
Human Lymphocytes ◽  
Normal Human

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.

scholarly journals Norfluoxetine Prevents Degeneration of Dopamine Neurons by Inhibiting Microglia-Derived Oxidative Stress in an MPTP Mouse Model of Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Kyung In Kim ◽  
Young Cheul Chung ◽  
Byung Kwan Jin
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Microglial Activation ◽  
Dopamine Neurons ◽  
Activated Microglia ◽  
Nigrostriatal Dopamine Neurons

Neuroinflammation is the neuropathological feature of Parkinson’s disease (PD) and causes microglial activation and activated microglia-derived oxidative stress in the PD patients and PD animal models, resulting in neurodegeneration. The present study examined whether norfluoxetine (a metabolite of fluoxetine) could regulate neuroinflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD and rescue dopamine neurons. Analysis by tyrosine hydroxylase (TH) immunohistochemistry demonstrated that norfluoxetine prevents degeneration of nigrostriatal dopamine neurons in vivo in MPTP-lesioned mice compared to vehicle-treated MPTP-lesioned control mice. MAC-1 immunostaining and hydroethidine histochemical staining showed that norfluoxetine neuroprotection is accompanied by inhibiting MPTP-induced microglial activation and activated microglia-derived reactive oxygen species production in vivo, respectively. In the separate experiments, treatment with norfluoxetine inhibited NADPH oxidase activation and nitrate production in LPS-treated cortical microglial cultures in vitro. Collectively, these in vivo and in vitro results suggest that norfluoxetine could be employed as a novel therapeutic agent for treating PD, which is associated with neuroinflammation and microglia-derived oxidative stress.

scholarly journals Etiology of Parkinson's Disease

2003 ◽  
Vol 30 (S1) ◽  
pp. S10-S18 ◽  
Author(s):  
Zhigao Huang ◽  
Raúl de la Fuente-Fernández ◽  
A. Jon Stoessl
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Environmental Factors ◽  
Neurodegenerative Disorders ◽  
Caffeine Intake ◽  
Genetic Mutations ◽  
Abnormal Protein ◽  
Relative Contribution ◽  
Genetic And Environmental Factors

There is growing recognition that Parkinson's disease (PD) is likely to arise from the combined effects of genetic predisposition as well as largely unidentified environmental factors. The relative contribution of each varies from one individual to another. Even in situations where more than one family member is affected, the predominant influence may be environmental. Although responsible for only a small minority of cases of PD, recently identified genetic mutations have provided tremendous insights into the basis for neurodegeneration and have led to growing recognition of the importance of abnormal protein handling in Parkinson's as well as other neurodegenerative disorders. Abnormal protein handling may increase susceptibility to oxidative stress; conversely, numerous other factors, including oxidative stress and impaired mitochondrial function can lead to impaired protein degradation. A limited number of environmental factors are known to be toxic to the substantia nigra; in contrast, some factors such as caffeine intake and cigarette smoking may protect against the development of PD, although the mechanisms are not established. We review the various genetic and environmental factors thought to be involved in PD, as well as the mechanisms that contribute to selective nigral cell death.

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