The Sources of Reactive Oxygen Species and Its Possible Role in the Pathogenesis of Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. The precise mechanism underlying pathogenesis of PD is not fully understood, but it has been widely accepted that excessive reactive oxygen species (ROS) are the key mediator of PD pathogenesis. The causative factors of PD such as gene mutation, neuroinflammation, and iron accumulation all could induce ROS generation, and the later would mediate the dopaminergic neuron death by causing oxidation protein, lipids, and other macromolecules in the cells. Obviously, it is of mechanistic and therapeutic significance to understand where ROS are derived and how ROS induce dopaminergic neuron damage. In the present review, we try to summarize and discuss the main source of ROS in PD and the key pathways through which ROS mediate DA neuron death.

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The Neuro-Protective Effects of the TSPO Ligands CB86 and CB204 on 6-OHDA-Induced PC12 Cell Death as an In Vitro Model for Parkinson’s Disease

Biology ◽

10.3390/biology10111183 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1183

Author(s):

Sheelu Monga ◽

Nunzio Denora ◽

Valentino Laquintana ◽

Rami Yashaev ◽

Abraham Weizman ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Death ◽

Neurodegenerative Disorder ◽

Reactive Oxygen ◽

Ros Generation ◽

Oxygen Species ◽

The Impact

Parkinson’s disease (PD) is a progressive neurodegenerative disorder which is characterized by the degeneration of dopaminergic neurons in substantia nigra (SN). Oxidative stress or reactive oxygen species (ROS) generation was suggested to play a role in this specific type of neurodegeneration. Therapeutic options which can target and counteract ROS generation may be of benefit. TSPO ligands are known to counteract with neuro-inflammation, ROS generation, apoptosis, and necrosis. In the current study, we investigated an in vitro cellular PD model by the assessment of 6-hydroxydopamine (6-OHDA, 80 µM)-induced PC12 neurotoxicity. Simultaneously to the exposure of the cells to 6-OHDA, we added the TSPO ligands CB86 and CB204 (25 µM each) and assessed the impact on several markers of cell death. The two ligands normalized significantly (57% and 52% respectively, from 44%; whereas the control was 68%) cell proliferation at different time points from 0–24 h. Additionally, we evaluated the effect of these two TSPO ligands on necrosis using propidium iodide (PI) staining and found that the ligands inhibited significantly the 6-OHDA-induced necrosis. As compared to control, the red count was increased up to 57-fold whereas CB86 and CB204 inhibited to 2.7-fold and 3.2-fold respectively. Necrosis was also analyzed by LDH assay which showed significant effect. Both assays demonstrated similar potent anti-necrotic effect of the two TSPO ligands. Reactive oxygen species (ROS) generation induced by 6-OHDA was also inhibited by the two TSPO ligand up to 1.3 and 1.5-fold respectively, as compared to 6-OHDA group. CB86 and CB204 inhibited also normalized the cell viability up to 1.8-fold after the exposure to 6-OHDA, as assessed by XTT assay. The two TSPO ligands also inhibited apoptosis significantly (1.3-fold for both) as assessed by apopxin green staining. In summary, it appears that the two TSPO ligands CB86 and CB204 can suppress cell death of PC12 induced by 6-OHDA. The results may be relevant to the use of these two TSPO ligands as therapeutic option neurodegenerative diseases like PD.

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Reactive Oxygen Species/Caspase 3 Promotes Autophagy of Nigral Dopaminergic Neuron in Parkinson’s Disease

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2542 ◽

2021 ◽

Vol 11 (2) ◽

pp. 320-325

Author(s):

Zejie Chen ◽

Yamin Wang ◽

Yanchun Yi ◽

Fengrong Liu

Keyword(s):

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protein Level ◽

Dopaminergic Neuron ◽

Caspase 3 ◽

Cell Model ◽

Reactive Oxygen ◽

Oxygen Species ◽

Bax Protein

Parkinson’s disease (PD) is characterized as bradykinesia and sleep disorder, troubling numerous people. In the present study, we aimed to explore whether reactive oxygen species (ROS)/caspase 3 promotes PD to provide a basis for novel treatments of PD. Firstly, we applied 1-methyl-4-phenylpyridinium (MPP+) to stimulate PC12 cell lines to establish a PD cell model. Western blot and qRT-PCR analyses detected protein and mRNA expression of caspase 3, IL-1β, Bax, and BCL2. Finally, ROS detection kit determined ROS content. Compared with the controls, MPP+-treated PC12 exhibited significantly elevated caspase 3, caspase 3, and IL-1β at the protein level (p < 0.001). In addition, MMP + treatment increased Bax protein level in vitro, while decreased Bcl-2 protein expression (p <0.001). Moreover, MPP + induced oxidative stress which contributes to autophagy. The ROS in MPP + group was increased significantly (p < 0.001). ROS and caspase 3 participate in the pathogenesis of PD and enhances autophagy of nigral dopaminergic neuron.

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Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species

International Journal of Molecular Sciences ◽

10.3390/ijms20143409 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3409 ◽

Cited By ~ 5

Author(s):

Yunseon Jang ◽

Hyosun Choo ◽

Min Joung Lee ◽

Jeongsu Han ◽

Soo Jeong Kim ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Mitochondrial Respiration ◽

Dopaminergic Neurons ◽

Reactive Oxygen ◽

Ros Generation ◽

Ros Production ◽

Oxygen Species

Current therapeutics for Parkinson’s disease (PD) are only effective in providing relief of symptoms such as rigidity, tremors and bradykinesia, and do not exert disease-modifying effects by directly modulating mitochondrial function. Here, we investigated auraptene (AUR) as a potent therapeutic reagent that specifically protects neurotoxin-induced reduction of mitochondrial respiration and inhibits reactive oxygen species (ROS) generation. Further, we explored the mechanism and potency of AUR in protecting dopaminergic neurons. Treatment with AUR significantly increased the viability of substantia nigra (SN)-derived SN4741 embryonic dopaminergic neuronal cells and reduced rotenone-induced mitochondrial ROS production. By inducing antioxidant enzymes AUR treatment also increased oxygen consumption rate. These results indicate that AUR exerts a protective effect against rotenone-induced mitochondrial oxidative damage. We further assessed AUR effects in vivo, investigating tyrosine hydroxylase (TH) expression in the striatum and substantia nigra of MPTP-induced PD model mice and behavioral changes after injection of AUR. AUR treatment improved movement, consistent with the observed increase in the number of dopaminergic neurons in the substantia nigra. These results demonstrate that AUR targets dual pathogenic mechanisms, enhancing mitochondrial respiration and attenuating ROS production, suggesting that the preventative potential of this natural compound could lead to improvement in PD-related neurobiological changes.

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Reactive Oxygen Species Affects on Mitochondrial Dynamicity Which May Leads to Parkinson’s Disease

SSRN Electronic Journal ◽

10.2139/ssrn.3573321 ◽

2020 ◽

Author(s):

Pallab Chakraborty

Keyword(s):

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Reactive Oxygen ◽

Oxygen Species

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Flavonoids, the Family of Plant-derived Antioxidants making inroads into Novel Therapeutic Design against IR-induced Oxidative Stress in Parkinson’s Disease

Current Neuropharmacology ◽

10.2174/1570159x19666210524152817 ◽

2021 ◽

Vol 19 ◽

Author(s):

Tapan Behl ◽

Gagandeep Kaur ◽

Aayush Sehgal ◽

Gokhan Zengin ◽

Sukhbir Singh ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Ionizing Radiation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Radiation Induced ◽

Novel Therapeutic

Background: Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various pieces of evidences assembled during preceding years reveal the pertinent role of ionizing radiation-induced oxidative stress in the progression of neurodegenerative insults such as Parkinson’s disease, which have been contributing to increased proliferation and generation of reactive oxygen species. Objective: This review delineates the role of ionizing radiation-induced oxidative stress in Parkinson’s disease and proposes novel therapeutic interventions of flavonoid family offering effective management and slowing down the progression of Parkinson’s disease. Method: Published papers were searched via MEDLINE, PubMed, etc. published to date for in-depth database collection. Results: The potential of oxidative damage may harm the non-targeted cells. It can also modulate the functions of central nervous system, such as protein misfolding, mitochondria dysfunction, increased levels of oxidized lipids, and dopaminergic cell death, which accelerates the progression of Parkinson’s disease at the molecular, cellular, or tissue levels. In Parkinson’s disease, reactive oxygen species exacerbate the production of nitric oxides and superoxides by activated microglia, rendering death of dopaminergic neuronal cell through different mechanisms. Conclusion: Rising interest has extensively engrossed on the clinical trial designs based on the plant derived family of antioxidants. They are known to exert multifarious impact either way in neuroprotection via directly suppressing ionizing radiation-induced oxidative stress and reactive oxygen species production or indirectly increasing the dopamine levels and activating the glial cells.

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Control of Reactive Oxygen Species for the Prevention of Parkinson’s Disease: The Possible Application of Flavonoids

Antioxidants ◽

10.3390/antiox9070583 ◽

2020 ◽

Vol 9 (7) ◽

pp. 583 ◽

Cited By ~ 6

Author(s):

Tae Yeon Kim ◽

Eunju Leem ◽

Jae Man Lee ◽

Sang Ryong Kim

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Glycogen Synthase ◽

Reactive Oxygen ◽

Adult Brain ◽

Related Factor ◽

Oxygen Species ◽

Antioxidant Defense Systems

Oxidative stress reflects an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense systems, and it can be associated with the pathogenesis and progression of neurodegenerative diseases such as multiple sclerosis, stroke, and Parkinson’s disease (PD). The application of antioxidants, which can defend against oxidative stress, is able to detoxify the reactive intermediates and prevent neurodegeneration resulting from excessive ROS production. There are many reports showing that numerous flavonoids, a large group of natural phenolic compounds, can act as antioxidants and the application of flavonoids has beneficial effects in the adult brain. For instance, it is well known that the long-term consumption of the green tea-derived flavonoids catechin and epigallocatechin gallate (EGCG) can attenuate the onset of PD. Also, flavonoids such as ampelopsin and pinocembrin can inhibit mitochondrial dysfunction and neuronal death through the regulation of gene expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Additionally, it is well established that many flavonoids exhibit anti-apoptosis and anti-inflammatory effects through cellular signaling pathways, such as those involving (ERK), glycogen synthase kinase-3β (GSK-3β), and (Akt), resulting in neuroprotection. In this review article, we have described the oxidative stress involved in PD and explained the therapeutic potential of flavonoids to protect the nigrostriatal DA system, which may be useful to prevent PD.

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