Role of Oxidative Stress in Parkinson's Disease

By O. Hwang. Experimental Neurobiology, 2013

1,478 citations recorded by the source corpus.

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder associated with a selective loss of the dopamine(DA)rgic neurons in the substantia nigra pars compacta and the degeneration of projecting nerve fibers in the striatum. Because there is currently no therapy that delays the neurodegenerative process, modification of the disease course by neuroprotective therapy is an important unmet clinical need. Toward this end, understanding cellular mechanisms that render the nigral neurons particularly vulnerable have been a subject of intensive research. Increasing evidence suggests that oxidative stress plays a major role. The metabolism of DA itself contributes to oxidative stress, resulting in modification of intracellular macromolecules whose functions are important for cell survival. Mitochondrial dysfunction and the consequent increase in reactive oxygen species also trigger a sequence of events that leads to cell demise. In addition, activated microglia produce nitric oxide and superoxide during neuroinflammatory responses, and this is aggravated by the molecules released by damaged DAergic neurons such as α-synuclein, neuromelanin and matrix metalloproteinase-3. Ways to reduce oxidative stress therefore can provide a therapeutic strategy. NAD(P)H:quinone reductase (NQO1) and other antioxidant enzymes, whose gene expression are commonly under the regulation of the transcription factor Nrf2, can serve as target proteins utilized toward development of disease-modifying therapy for PD.

Subfields: Cellular and Molecular Neuroscience, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/2128288365a99e23f83ddc6704ba9d8c4dffb462

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. O. Maier
2. Roman Fischer
3. L. Zuo
4. Zewen Liu
5. M. Duennwald
6. Vy Ngo
7. Tingyang Zhou

In Neurology

1. O. Maier
2. Roman Fischer
3. L. Zuo
4. Zewen Liu
5. M. Duennwald
6. Vy Ngo
7. Tingyang Zhou

In Physiology

1. O. Maier
2. Roman Fischer
3. L. Zuo
4. Zewen Liu
5. P. Dimitrion
6. M. Duennwald
7. Alexander C Ziegler
8. Vy Ngo

Citations in the corpus

• Interrelation of Oxidative Stress and Inflammation in Neurodegenerative Disease: Role of TNF (2015, background): “For example, it has been shown that astrogliosis in the substantia nigra leads to local activation of microglia in PD [17, 76].”
• Mechanisms of DNA damage, repair and mutagenesis (2017, neutral): “Despite this, an overabundance of ROS species is notably associated with the development of human diseases, such as cancer, Alzheimer’s disease, Parkinson’s disease, diabetes, and heart failure [Giacco and Brownlee, 2010; Liou and Storz, 2010; Mohsenzadegan and Mirshafiey, 2012; Dias et al., 2013; H”
• Mitochondrial electron transport chain, ROS generation and uncoupling (Review) (2019, background): “Various studies link UcP2 with neurodegeneration and aging (123,124,219).”
• Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications (2017, background): “ROS have been shown to contribute significantly to dopaminergic neuronal loss (Figure 1) [14, 95].”
• Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022, background): “Oxidative damage has been implicated in all major neurodegenerative diseases including Alzheimer’s disease (AD) [108,109], Parkinson’s disease (PD) [110,111], Huntington’s disease (HD) [112,113], amyotrophic lateral sclerosis (ALS) [114], and multiple sclerosis (MS) [115].”
• Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections (2023, background): “Recent reviews emphasizing the close association between hyperglycemia, oxidative stress and inflammation have been published in a number of human metabolic dysfunctions and pathologies related to the liver [15,16], adipose tissue [17], skeletal muscle [18,19], kidney [20,21], cardiovascular system ”
• Oxidative Stress: A Key Modulator in Neurodegenerative Diseases (2019, background): “PD is the second most common neurodegenerative disorder after AD in elderly people characterized by selective neuronal impairment of dopaminergic (DA) neurons in the substantia nigra pas compacta (SNc), along with the reduction of DA levels in the nigrostriatal DA pathway in the brain [95].”
• Role of ROS and Nutritional Antioxidants in Human Diseases (2018, background): “Numerous studies have been performed to investigate the therapeutic effects of natural antioxidants on neurodegenerative disorders; however, mixed results have been yielded (Dias et al., 2013; Yan et al., 2013).”