Industrial toxicants and Parkinson's disease

Caudle, W. Michael; Guillot, Thomas S.; Lazo, Carlos R.; Miller, Gary W.

doi:10.1016/j.neuro.2012.01.010

Cited by 128 publications

(104 citation statements)

References 144 publications

(152 reference statements)

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“…As we and others have recently reviewed, several classes of compounds have been associated with PD pathology, especially halogenated persistent organic pollutants (POPs) [16, 100, 101]. Halogenated POPs represent a broad class of environmental toxicants that include organochlorine insecticides, polychlorinated biphenyls (PCBs), and brominated flame retardants.…”

Section: Toxicological Blockade Of Vmat2mentioning

confidence: 99%

Vesicular Integrity in Parkinson’s Disease

Alter

Lenzi

Bernstein

et al. 2013

Curr Neurol Neurosci Rep

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The defining motor characteristics of Parkinson’s disease (PD) are mediated by the neurotransmitter dopamine (DA). Dopamine molecules spend most of their lifespan stored in intracellular vesicles awaiting release and very little time in the extracellular space or the cytosol. Without proper packaging of transmitter and trafficking of vesicles to the active zone, dopamine neurotransmission cannot occur. In the cytosol, dopamine is readily oxidized; excessive cytosolic dopamine oxidation may be pathogenic to nigral neurons in PD. Thus, factors that disrupt vesicular function may impair signaling and increase the vulnerability of dopamine neurons. This review outlines the many mechanisms by which disruption of vesicular function may contribute to the pathogenesis of PD. From direct inhibition of dopamine transport into vesicles by pharmacological or toxicological agents to alterations in vesicle trafficking by PD-related gene products, variations in the proper compartmentalization of dopamine can wreak havoc on a functional dopamine pathway. Findings from patient populations, imaging studies, transgenic models, and mechanistic studies will be presented to document the relationship between impaired vesicular function and vulnerability of the nigrostriatal dopamine system. Given the deleterious effects of impaired vesicular function, strategies aimed at enhancing vesicular function may be beneficial in the treatment of PD.

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Section: Toxicological Blockade Of Vmat2mentioning

confidence: 99%

Vesicular Integrity in Parkinson’s Disease

Alter

Lenzi

Bernstein

et al. 2013

Curr Neurol Neurosci Rep

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“…Metal exposure has been considered a major chemical risk factor in the pathogenesis of chronic neurodegenerative conditions such as Parkinson’s disease (PD) (Dobson et al, 2004, Aschner et al, 2009, Furbee, 2011, Caudle et al, 2012, Kanthasamy et al, 2012). PD imposes an estimated economic burden of $23 billion per year in the United States alone (Weintraub et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Vanadium exposure induces olfactory dysfunction in an animal model of metal neurotoxicity

et al. 2014

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Epidemiological evidence indicates chronic environmental exposure to transition metals may play a role in chronic neurodegenerative conditions such as Parkinson’s disease (PD). Chronic inhalation exposure to welding fumes containing metal mixtures may be associated with development of PD. A significant amount of vanadium is present in welding fumes, as vanadium pentoxide (V2O5), and incorporation of vanadium in the production of high strength steel has become more common. Despite the increased vanadium use in recent years, the neurotoxicological effects of this metal are not well characterized. Recently, we demonstrated that V2O5 induces dopaminergic neurotoxicity via protein kinase C delta (PKCδ)-dependent oxidative signaling mechanisms in dopaminergic neuronal cells. Since anosmia (inability to perceive odors) and non-motor deficits are considered to be early symptoms of neurological diseases, in the present study, we examined the effect of V2O5 on the olfactory bulb in animal models. To mimic the inhalation exposure, we intranasally administered C57 black mice a low-dose of 182 µg of V2O5 three times a week for one month, and behavioral, neurochemical and biochemical studies were performed. Our results revealed a significant decrease in olfactory bulb weights, tyrosine hydroxylase (TH) levels, levels of dopamine (DA) and its metabolite, 3, 4-dihydroxyphenylacetic acid (DOPAC) and increases in astroglia of the glomerular layer of the olfactory bulb in the treatment groups relative to vehicle controls. Neurochemical changes were accompanied by impaired olfaction and locomotion. These findings suggest that nasal exposure to V2O5 adversely affects olfactory bulbs, resulting in neurobehavioral and neurochemical impairments. These results expand our understanding of vanadium neurotoxicity in environmentally-linked neurological conditions.

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“…21 Once in brain tissue, Mn can induce neuronal damage that potentially can culminate in PS/PD. 22 In the next section of this chapter we will summarize evidence derived from epidemiological studies of PS/PD among welders, who represent a segment of the working population with particularly high Mn exposures. Our review is not intended to be comprehensive, but rather is restricted to literature that we regard as most informative.…”

Section: Manganese and Parkinsonism: Historical Backgroundmentioning

confidence: 99%

Epidemiological Studies of Parkinsonism in Welders

Checkoway¹,

Nielsen²,

Racette³

2014

Manganese in Health and Disease

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Welders have been the focus of numerous epidemiological studies addressing possible etiologic relations between manganese (Mn) and Parkinson disease (PD). These include investigations of defined cohorts of welders, which we regard as most informative, general population surveys of welding occupations, and population-based case-control studies. With a few notable exceptions among the studies of defined cohorts of welders, there is little evidence that welders are at increased risk of PD. However, most prior research has suffered from severe limitations due to incomplete ascertainment of incident cases, questionable diagnostic accuracy, and non-specific Mn exposure assessment that precludes quantitative dose–response estimation. A potential etiologic relation between environmental Mn exposure and PD continues to be an important scientific and public health topic, given the ubiquitous nature of Mn exposure. Investigations of welders, who experience some of the highest Mn doses in the population, should remain a priority. Recommended future epidemiological research should involve longitudinal assessments of risk, severity, and progression of clinically diagnosed PD among well-characterized cohorts of welders, whose exposures to Mn and potential confounders can be assessed quantitatively.

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Industrial toxicants and Parkinson's disease

Cited by 128 publications

References 144 publications

Vesicular Integrity in Parkinson’s Disease

Vesicular Integrity in Parkinson’s Disease

Vanadium exposure induces olfactory dysfunction in an animal model of metal neurotoxicity

Epidemiological Studies of Parkinsonism in Welders

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