Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Perfeito, Rita; Cunha‐Oliveira, Teresa; Rego, A. Cristina

doi:10.1016/j.freeradbiomed.2012.08.569

Cited by 93 publications

(65 citation statements)

References 308 publications

(253 reference statements)

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“…24,[70][71][72][74][75][76][77][78][79][80][81] Because PON1 is capable of hydrolyzing toxic organophosphates and also has an important antioxidant capacity, the association of PON polymorphisms and PD has been addressed by multiple authors. The frequency of the Met 54 allele of PON1 has been found to be significantly higher in patients with PD compared with control subjects.…”

Section: 70-73mentioning

confidence: 99%

“…Conversely, there seems to be more solid evidence suggesting that when there is exposure to a toxic environment there is a correlation between the presence of certain genotypes and the development of the disease. 24,70,[73][74][75][76]79,91 PON1, Alzheimer's disease, and other dementias Across the world, the prevalence of dementia is believed to be 24 million, and is expected to double every 20 years until 2040. 26 AD is the foremost cause of dementia starting with compromised memory.…”

Section: 70-73mentioning

confidence: 99%

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Paraoxonase 1 in neurological disorders

Menini

Gugliucci

2013

Redox Report

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Paroxonase 1 displays multiple physiological activities that position it as a putative player in the pathogenesis of neurological disorders. Here we reviewed the literature focusing on the role of paraoxonase 1 (PON1) as a factor in the risk of stroke and the major neurodegenerative diseases. PON1 activity is reduced in stroke patients, which significantly correlates inversely with carotid and cerebral atherosclerosis. The presence of the R allele of the Q192R PON1 polymorphism seems to potentiate this risk for stroke. PON1 exerts peroxidase activities that may be important in neurodegenerative disorders associated with oxidative stress. PON1 is also a key detoxifier of organophosphates and organophosphate exposure has been linked to the development of neurological disorders in which acetylcholine plays a significant role. In Parkinson's disease most of the studies suggest no participation of either L55M or the Q192R polymorphisms in its pathogenesis. However, many studies suggest that the MM55 PON1 genotype is associated with a higher risk for Parkinson's disease in individuals exposed to organophosphates. In Alzheimer's disease most studies have failed to find any association between PON1 polymorphisms and the development of the disease. Some studies show that PON1 activity is decreased in patients with Alzheimer's disease or other dementias, suggesting a possible protective role of PON1. No links between PON1 polymorphisms or activity have been found in other neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis. PON1 is a potential player in the pathogenesis of several neurological disorders. More research is warranted to ascertain the precise pathogenic links and the prognostic value of its measurement in neurological patients.

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Section: 70-73mentioning

confidence: 99%

Section: 70-73mentioning

confidence: 99%

Paraoxonase 1 in neurological disorders

Menini

Gugliucci

2013

Redox Report

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“…For example, the cellular toxicity associated with chronic Amp (73) and chronic exposure to high levels of air pollutants has been attributed to oxidative stress (56). In the case of the amphetamines, the oxidative stress induced by DA quinone and its redox activity has been proposed to be the basis for cellular oxidation (54,55). Air pollutant effects are also attributed to the components of the particle phase, which we have shown are primarily prooxidant.…”

Section: Discussionmentioning

confidence: 74%

“…These PD/PK studies provided further support for the exchange diffusion model for neurotransmitter release by the amphetamines, instead of a depolarization and neuronal release process for the stimulation of the postsynaptic receptors. The resultant micromolar concentrations of catecholamines and 5-HT present in extracellular space and their ability to generate hydrogen peroxide provided a mechanism by which neuronal damage may occur during a protracted abuse period; its role in a model of DA neurotoxicity has been reviewed recently (54,55).…”

Section: Amphetamine and Methamphetaminementioning

confidence: 99%

A Chemical Perspective of Pharmacology and Toxicology

Cho

2018

Annu. Rev. Pharmacol. Toxicol.

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My chemical training provided a somewhat different perspective of biological problems, in the problem itself and approaches to its solution. I was fortunate to have in my laboratory postdocs and students who shared this perspective and used appropriate tools to address problems in amphetamine pharmacology and air pollution toxicology. These apparently disparate areas of research shared two chemical reactions: prooxidant-based generation of reactive oxygen and formation of covalent bonds between electrophiles and biological nucleophiles. This article is an attempt to summarize that research and to identify those individuals who made the contributions.

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“…Parkinson disease (PD) is the second most prevalent neurodegenerative disorder, affecting 1 to 2% of the population above 65 years of age and, approximately, 4% of individuals above 85 years (Perfeito, Oliveira, Rego, 2012). The clinical symptoms of PD manifest as the loss of initiation and control of movement, which appear after a substantial loss of dopaminergic neurons (50-60%) in the substantia nigra pars compacta (SNpc).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the antioxidant potential of antiparkinsonian drugs in different in vitro models

Farias

Bonifácio

Matsumoto

et al. 2014

Braz. J. Pharm. Sci.

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Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Furthermore, oxidative stress plays a role in PD, causing or contributing to the neurodegenerative process. Currently PD has only symptomatic treatment and still nothing can be done to stop the degenerative process of the disease. This study aimed to comparatively evaluate the antioxidant capacity of pramipexole, selegeline and amantadine in different in vitro studies and to offer possible explanations on the molecular antioxidant mechanisms of these drugs. In vitro, the antioxidant capacity of the drugs was assessed by the ability of antiparkinsonian drugs to decrease or scavenge ROS in the neutrophil respiratory burst, ability of antiparkinsonian drugs to donate hydrogen and stabilize the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH•), to scavenge 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid (ABTS + ) and evaluation of the ferric reducing antioxidant power (FRAP). This study demonstrated that both pramipexole and selegiline, but not amantadine, have antioxidant effects in vitro by scavenging superoxide anion on the respiratory burst, donating electron in the ABTS + assay and presenting ferric reduction antioxidant power. This chemical structure-related antioxidant capacity suggests a possible neuroprotective mechanism of these drugs beyond their already recognized mechanism of action.Uniterms: Parkinson´s disease. Oxidative stress. Antiparkinsonian drugs/in vitro studies. Antioxidants.A doença de Parkinson (DP) é caracterizada pela degeneração progressiva dos neurônios dopaminérgicos na substância negra pars compacta. Além disso, o estresse oxidativo, presente nesta doença, causa ou contribui para o processo neurodegenerativo. Atualmente, a DP tem apenas tratamento sintomático e ainda nada pode ser feito para interromper o processo degenerativo. Este estudo teve como objetivo avaliar, comparativamente, a capacidade antioxidante do pramipexol, selegilina e amantadina em diferentes testes in vitro e oferecer possíveis explicações sobre os mecanismos moleculares antioxidantes destes fármacos. Avaliou-se a atividade antioxidante dos fármacos através da capacidade em diminuir ou sequestrar espécies reativas de oxigênio no burst respiratório, da capacidade em doar hidrogênio e estabilizar o radical livre 2,2-difenil-1-picril-hidrazil (DPPH•), de remover o radical 2,2'-azino-di-(3-etilbenzotiazolina-6-sulfônico (ABTS + ) e da verificação do poder redutor/antioxidante do ferro (FRAP). Este estudo demonstrou que tanto o pramipexol como a selegilina, mas não a amantadina, possuem efeitos antioxidantes in vitro por eliminar o ânion superóxido no burst respiratório, doar elétrons no método ABTS e apresentar poder redutor sobre o ferro (FRAP). Essa capacidade antioxidante pode estar relacionada com a estrutura química desses medicamentos, sugerindo possíveis mecanismos neuroprotetores destes fármacos além de seus mecanismos de ação já conhecidos. Unitermos: Doença de Parkinson. ...

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Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Cited by 93 publications

References 308 publications

Paraoxonase 1 in neurological disorders

Paraoxonase 1 in neurological disorders

A Chemical Perspective of Pharmacology and Toxicology

Comparison of the antioxidant potential of antiparkinsonian drugs in different in vitro models

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