Parkinson's Disease

Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease - Underscores that only a small fraction of the disease can be blamed on genes and that  environmental factors , including certain pesticides, almost certainly play an important role in this disorder. This ALDH model for PD etiology may help explain the selective vulnerability of dopaminergic neurons in PD and provide a potential mechanism through which environmental toxicants contribute to PD pathogenesis; Fitzmaurice AG, Rhodes SL, Lulla A, Murphy NP, Lam HA, O'Donnell KC, Barnhill L, Casida JE, Cockburn M, Sagasti A, Stahl MC, Maidment NT, Ritz B,Bronstein JM; Department of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles; Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):636-41.

Developmental exposure to pesticides zineb and/or endosulfan renders the nigrostriatal dopamine system more susceptible to these environmental chemicals later in life. - Findings support our hypothesis that exposure to pesticides such as endosulfan and zineb during critical periods of postnatal development contributes to neurotransmitter changes upon re-challenge in adulthood.[Jia, Z., et al. 2007. Neurotoxicology 28(4):727-735]

Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids. - Study suggests that neonatal exposition to permethrin or cypermethrin induces long-lasting effects.[Nasuti C, Gabbianelli R, Falcioni ML, et al.2007. Toxicology. 229(3):194-205.]

Dopamine Transporter Genetic Variants and Pesticides in Parkinson’s Disease. - Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold, and in carriers of two or more alleles more than 4-fold. [Ritz BR, et al. 2009. Environ Health Perspect 117(6)]

Environmental Risk Factors and Parkinson's Disease: A Metaanalysis - Findings suggest that living in a rural area, drinking well water, farming, and exposure to pesticides may be a risk factor for developing PD. [Priyadarshi, A., et al. 2001.Environ Res 86(2):122-127

Exposure to home pesticides linked to Parkinson disease. - Respondents who reported handling or applying herbicides for up to 30 days are 40 percent more likely to develop the disease, whereas respondents that reported 160 days exposure, have a 70 percent increase.[Stephenson, J. 2000. JAMA 283:3055-3056]

Exposure to pesticides or solvents and risk of Parkinson disease - The literature supports the hypothesis that exposure to pesticides or solvents is a risk factor for PD. Further prospective and high-quality case-control studies are required to substantiate a cause-effect relationship. Gianni Pezzoli, MD, Emanuele Cereda, MD, PhD; Neurology May 28, 2013 vol. 80 no. 22 2035-2041

Genetic modification of the association of paraquat and Parkinson's disease - Findings suggest that PD risk from paraquat exposure might be particularly high in individuals lacking GSTT1. GSTT1*0 is common and could potentially identify a large subpopulation at high risk of PD from oxidative stressors such as paraquat.[Goldman, S, Kamel, F, Webster Ross, G, et al. 2012. Movement Disorders. 27(13):1652-1658]

Isogenic Human iPSC Parkinson’s Model Shows Nitrosative Stress-Induced Dysfunction in MEF2-PGC1α Transcription - Parkinson’s disease (PD) is characterized by loss of A9 dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). An association has been reported between PD and exposure to mitochondrial toxins, including environmental pesticides paraquat, maneb, and rotenone. Here, using a robust, patient-derived stem cell model of PD allowing comparison of A53T α-synuclein (α-syn) mutant cells and isogenic mutation-corrected controls, we identify mitochondrial toxin-induced perturbations in A53T α-syn A9 DA neurons (hNs). We report a pathway whereby basal and toxin-induced nitrosative/oxidative stress results in S-nitrosylation of transcription factor MEF2C in A53T hNs compared to corrected controls. This redox reaction inhibits the MEF2C-PGC1α transcriptional network, contributing to mitochondrial dysfunction and apoptotic cell death. Our data provide mechanistic insight into gene-environmental interaction (GxE) in the pathogenesis of PD. Furthermore, using small-molecule high-throughput screening, we identify the MEF2C-PGC1α pathway as a therapeutic target to combat PD.

Is Pesticide Use Related to Parkinson Disease? Some Clues to Heterogeneity in Study Results . - This review affirms the evidence that exposure to herbicides and insecticides increase the risk of PD. Future studies should focus on more objective and improved methods of pesticide exposure assessment.[van der Mark, M, Brouwer, M et al. 2012. Environ Health Perspect. 120(3):340-347]

Neurodegenerative Diseases and Exposure to Pesticides in the Elderly - These results suggest the presence of neurologic impairments in elderly persons who were exposed occupationally to pesticides.[Baldi, I., et al. 2003. American Journal of Epidemiology 157(5):409-414]

Nitration of microtubules blocks axonal mitochondrial transport in a human pluripotent stem cell model of Parkinson’s disease - Morgan G. Stykel, Kayla Humphries, Mathew P. Kirby, Chris Czaniecki, Tinya Wang, Tammy Ryan, Vladimir Bamm, and Scott D. Ryan

No evidence for heritability of Parkinson disease in Swedish twins - Results suggest that environmental factors are most important in the etiology of PD. Compared with other complex diseases, the importance of genetic effects in PD is notably low. [Wirdefeldt, K., et al. 2004. Neurology 63(2):305-311]

Occupational exposure to pesticides and Parkinson's disease: A systematic review and meta-analysis of cohort studies. - Study concludes that there is support for the hypothesis that occupational exposure to pesticides increases the risk of PD.[Van Maele-Fabry, G, Hoet, P, Vilain, F and Lison, D. 2012. Envrionment International. 46:30-43]

Occupational pesticide use and Parkinson's disease in the Parkinson Environment Gene (PEG) study. - Narayan S, Liew Z, Bronstein JM, Ritz B

Paraoxonase 1, agricultural organophosphate exposure, and Parkinson disease - Study found that participants with two copies of a common gene variant showed an increased risk of Parkinson's disease (PD) when exposed to pesticides used in agriculture. Participants with the MM PON1-55 genotype and exposed to diazinon or chlorpyrifos showed a twofold increased risk of Parkinson's disease (PD) compared to exposed subjects with wildtype genotype or only one variant copy or non-pesticide exposed subjects. [Manthripragada AD, et al. 2010. Epidemiology 21(1):87-94]

Parkinson’s 'cluster' prompts calls for further pesticide research - original study: Monash University and the Florey Institute of Neuroscience and Mental Health

Parkinson’s Disease in Louisiana, 1999–2012: Based on Hospital Primary Discharge Diagnoses, Incidence, and Risk in Relation to Local Agricultural Crops, Pesticides, and Aquifer Recharge - Martin E. Hugh-Jones, R. Hampton Peele, and Vincent L. Wilson

Parkinson’s Disease in Louisiana, 1999–2012: Based on Hospital Primary Discharge Diagnoses, Incidence, and Risk in Relation to Local Agricultural Crops, Pesticides, and Aquifer Recharge - Martin E. Hugh-Jones, R. Hampton Peele, and Vincent L. Wilson

Parkinson’s disease risk from ambient exposure to pesticides - Finds that people whose workplaces were close to fields sprayed with chemicals — not just those who live nearby — are at higher risk of developing Parkinson’s disease (PD). Those exposed to ziram, maneb, and paraquat together experienced the greatest increase in PD risk. Results suggest that pesticides affecting different mechanisms that contribute to dopaminergic neuron death may act together to increase the risk of PD considerably.[Wang A, et al. 2011. Eur J Epidemiol. DOI: 10.1007/s10654-011-9574-5]

Pesticide exposure and risk for Parkinson's disease - These data support the hypothesis that exposure to pesticides may increase risk for PD.  [Ascherio, Al, et al. 2006. Annals of Neurology 60(2): 197-203.]

Pesticide exposure and self-reported Parkinson's disease in the agricultural health study. - This study suggests that exposure to certain pesticides may increase PD risk.  [Kamel, F., et al. 2007. American Journal of Epidemiology 165(4):364-74]

Pesticides and Parkinson’s Disease—Is There a Link? - A comprehensive review of the published epidemiologic and toxicologic literature and critical evaluation of whether a relationship exists between pesticide exposure and PD. From the epidemiologic literature, there does appear to be a relatively consistent relationship between pesticide exposure and PD. This relationship appears strongest for exposure to herbicides and insecticides, and after long durations of exposure.[Brown, T.P., et al. 2006. Environmental Health Perspectives 114(2):156-164]

Pesticides and risk of Parkinson disease: a population-based case-control study. - Study investigated associations between pesticide exposures and idiopathic PD and found significantly increased ORs from lifelong well water consumption . [ J.A., et al. 2005. Archives of Neurology 62(1):91-95]

Professional exposure to pesticides and Parkinson disease - Study found a positive association between PD and overall professional pesticide use  with a dose-effect relation for the number of years of use  Results support an association between PD and professional pesticide exposure, and show that some pesticides (ie, organochlorine insecticides) may be more particularly involved. [Elbaz, A.et al. 2009. Ann Neurol;66:494-504]

Rotenone, Paraquat and Parkinson's Disease - PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally: those which impair mitochondrial function and those which increase oxidative stress, supporting a role for these mechanisms in PD pathophysiology.[Tanner, CM. et al. 2011. Environ Health Perspect.doi:10.1289/ehp.1002839]

Well-Water Consumption and Parkinson’s Disease in Rural California - High levels of possible well-water contamination with methomyl, chlorpyrifos, and propargite resulted in approximately 70–90% increases in relative risk of PD. Exposure to a higher number of water-soluble pesticides and organophosphate pesticides also increased the relative risk of PD. [Gatto NM, et al. 2009. Environ Health Perspect 117:1912-1918]