Pesticides, Microglial NOX2, and Parkinson's Disease

Taetzsch, Thomas; Block, Michelle L.

doi:10.1002/jbt.21464

Cited by 53 publications

(44 citation statements)

References 174 publications

(249 reference statements)

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“…In particular, the role of NOX2 in microglia leads to ROS generation, which, ultimately, damages neurons. Both mechanisms were described in models of PD (45,164). As of today, sequences of events that are driven by NOX-derived ROS, leading to neurodegeneration, are mostly hypothetical.…”

Section: Neurodegenerative Disordersmentioning

confidence: 99%

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New Insights on NOX Enzymes in the Central Nervous System

Nayernia

Jaquet

Krause

2014

Antioxidants & Redox Signaling

235

219

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Significance: There is increasing evidence that the generation of reactive oxygen species (ROS) in the central nervous system (CNS) involves the NOX family of nicotinamide adenine dinucleotide phosphate oxidases. Controlled ROS generation appears necessary for optimal functioning of the CNS through fine-tuning of redoxsensitive signaling pathways, while overshooting ROS generation will lead to oxidative stress and CNS disease. Recent Advances: NOX enzymes are not only restricted to microglia (i.e. brain phagocytes) but also expressed in neurons, astrocytes, and the neurovascular system. NOX enzymes are involved in CNS development, neural stem cell biology, and the function of mature neurons. While NOX2 appears to be a major source of pathological oxidative stress in the CNS, other NOX isoforms might also be of importance, for example, NOX4 in stroke. Globally speaking, there is now convincing evidence for a role of NOX enzymes in various neurodegenerative diseases, cerebrovascular diseases, and psychosis-related disorders. Critical Issues: The relative importance of specific ROS sources (e.g., NOX enzymes vs. mitochondria; NOX2 vs. NOX4) in different pathological processes needs further investigation. The absence of specific inhibitors limits the possibility to investigate specific therapeutic strategies. The uncritical use of non-specific inhibitors (e.g., apocynin, diphenylene iodonium) and poorly validated antibodies may lead to misleading conclusions. Future Directions: Physiological and pathophysiological studies with cell-type-specific knock-out mice will be necessary to delineate the precise functions of NOX enzymes and their implications in pathomechanisms. The development of CNS-permeant, specific NOX inhibitors will be necessary to advance toward therapeutic applications. Antioxid. Redox Signal. 20, 2815Signal. 20, -2837

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Section: Neurodegenerative Disordersmentioning

confidence: 99%

“…ROS and microglia activation are known to contribute to DA neuron death (134). A comprehensive review describing the key role of NOX2 and microglia activation in the neurodegeneration of DA neurons of the substantia nigra was recently published (164).…”

Section: Studies In Humansmentioning

confidence: 99%

New Insights on NOX Enzymes in the Central Nervous System

Nayernia

Jaquet

Krause

2014

Antioxidants & Redox Signaling

235

219

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“…Increasing evidence has indicated that rotenone exposure is associated with an increased risk of developing Parkinson's disease (PD) [25].…”

Section: Discussionmentioning

confidence: 99%

Behavioral Studies of Wistar Rats in Rotenone Induced Model of Parkinson’s Disease

Priyanga

Krishnamurthy

Selvaraj

2017

Int J Pharm Pharm Sci

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Objective: The objective of the study was to determine the behavioral activities of Wistar rats induced with rotenone.Methods: Thirty-six male Wistar rats were taken for the study and divided into six groups of six rats each. Group-I is the vehicle-treated, Group-II animals were induced with rotenone (3 mg/kg/bwt) by i. p. Group-III were co-treated with rotenone and L-DOPA (10 mg/kg/bwt) orally, Group-IV were co-treated with rotenone and quercetin (25 mg/kg/bwt) orally, Group-V were co-treated with rotenone and hesperidin (50 mg/kg/bwt) orally, Group-VI were treated with rotenone, quercetin and hesperidin in the same dosage regime for 60 d. The behavioural tests, such as open field test, ladder climbing test and hanging wire test were performed. The biochemical parameters such as urea, creatinine and activities of ALT and AST were also analysed.Results: All data are expressed as the mean±SD. Disability was noted in the behaviour of rats induced with Parkinson's disease (PD). The deficits in behavioral activity were significantly changed when compared with an induced group (p<0.001) and biochemical parameters due to rotenone were significantly (p<0.001) restored by co-treatment with quercetin and hesperidin. Conclusion:In our in vivo study, we have demonstrated the combination of quercetin and hesperidin to serve as neuroprotective compounds by improving the behavioral abnormalities and restoring the biochemical parameters. Hence, these powerful antioxidants may protect brain cells.

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“…Significant associations between pesticide exposure and cancer have been previously described (51,82–88). However, the exposure to pesticides may also cause the development of other pathological conditions, such as amyotrophic lateral sclerosis (89), asthma (90), type II diabetes (89), and Alzheimer's and Parkinson's disease (92,93). …”

Section: Pesticidesmentioning

confidence: 99%

Occupational exposure to carcinogens: Benzene, pesticides and fibers

Falzone

Marconi

Loreto

et al. 2016

Molecular Medicine Reports

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It is well known that the occupational exposure to contaminants and carcinogens leads to the development of cancer in exposed workers. In the 18th century, Percivall Pott was the first to hypothesize that chronic exposure to dust in the London chimney sweeps was associated with an increased risk of developing cancer. Subsequently a growing body of evidence indicated that other physical factors were also responsible for oncogenic mutations. Over the past decades, many carcinogens have been found in the occupational environment and their presence is often associated with an increased incidence of cancer. Occupational exposure involves several factors and the association between carcinogens, occupational exposure and cancer is still unclear. Only a fraction of factors is recognized as occupational carcinogens and for each factor, there is an increased risk of cancer development associated with a specific work activity. According to the International Agency for Research on Cancer (IARC), the majority of carcinogens are classified as ‘probable’ and ‘possible’ human carcinogens, while, direct evidence of carcinogenicity is provided in epidemiological and experimental studies. In the present review, exposures to benzene, pesticides and mineral fibers are discussed as the most important cancer risk factors during work activities.

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Pesticides, Microglial NOX2, and Parkinson's Disease

Cited by 53 publications

References 174 publications

New Insights on NOX Enzymes in the Central Nervous System

New Insights on NOX Enzymes in the Central Nervous System

Behavioral Studies of Wistar Rats in Rotenone Induced Model of Parkinson’s Disease

Occupational exposure to carcinogens: Benzene, pesticides and fibers

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