scholarly journals Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease

10.3791/50960 ◽  
2014 ◽  
Author(s):  
Vivian P. Chou ◽  
Novie Ko ◽  
Theodore R. Holman ◽  
Amy B. Manning-Boğ
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Environment Interaction ◽  
Interaction Models ◽  
Gene Environment Interaction ◽  
Gene Environment

Gene-Gene and Gene-Environment Interaction on the Risk of Parkinson’s Disease

2014 ◽  
Vol 7 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Neeraj Singh ◽  
Basu Banerjee ◽  
Kiran Bala ◽  
Mitrabasu Chhillar ◽  
Neelam Chhillar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment

435: Gene-Environment Interaction in Parkinson's Disease

2005 ◽  
Vol 161 (Supplement_1) ◽  
pp. S109-S109
Author(s):  
E McCanlies ◽  
G Murphy ◽  
D Fekedulegn ◽  
G W Ross ◽  
C M Burchfiel
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment

scholarly journals Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease

2016 ◽  
Vol 32 ◽  
pp. 25-30 ◽  
Author(s):  
Joanna M. Biernacka ◽  
Sun Ju Chung ◽  
Sebastian M. Armasu ◽  
Kari S. Anderson ◽  
Christina M. Lill ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pesticide Exposure ◽  
Interaction Analysis ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Genome Wide

scholarly journals Population genetic approaches to neurological disease: Parkinson's disease as an example

2005 ◽  
Vol 360 (1460) ◽  
pp. 1573-1578 ◽  
Author(s):  
S Gandhi ◽  
P.M Abou-Sleiman ◽  
D.G Healy ◽  
M Weale ◽  
W Gilks ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Xenobiotic Enzymes ◽  
Drug Metabolizing Enzyme ◽  
Gene Environment ◽  
Tremendous Progress ◽  
Different Populations ◽  
Metabolizing Enzyme

Parkinson's disease (PD) is a common, progressive, incurable disabling condition. The cause is unknown but over the past few years tremendous progress in our understanding of the genetic bases of this condition has been made. To date, this has almost exclusively come from the study of relatively rare Mendelian forms of the disease and there are no currently, widely accepted common variants known to increase susceptibility. The role that the ‘Mendelian’ genes play in common sporadic forms of PD is unknown. Moreover, most studies in PD can really be described as candidate polymorphism studies rather than true and complete assessments of the genes themselves. We provide a model of how one might tackle some of these issues using Parkinson's disease as an illustration. One of the emerging hypotheses of gene environment interaction in Parkinson's disease is based on drug metabolizing (or xenobiotic) enzymes and their interaction with putative environmental toxins. This motivated us to describe a tagging approach for an extensive but not exhaustive list of 55 drug metabolizing enzyme genes. We use these data to illustrate the power, and some of the limitations of a haplotype tagging approach. We show that haplotype tagging is extremely efficient and works well with only a modest increase in effort through different populations. The tagging approach works much less well if the minor allele frequency is below 5%. However, it will now be possible using these tags to evaluate these genes comprehensively in PD and other neurodegenerative conditions.

scholarly journals The industrial solvent trichloroethylene induces LRRK2 kinase activity and dopaminergic neurodegeneration in a rat model of Parkinson’s disease

2020 ◽  
Author(s):  
Sandra L. Castro ◽  
Emily M. Rocha ◽  
Christopher R. Bodle ◽  
Katrina E. Johnson ◽  
J. Timothy Greenamyre ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Organic Solvents ◽  
Dopaminergic Neurons ◽  
Kinase Activity ◽  
Environment Interaction ◽  
Dopaminergic Neurodegeneration ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Lrrk2 Kinase ◽  
Lrrk2 Kinase Activity

Gene-environment interaction is implicated in the majority of idiopathic Parkinson’s disease (PD) risk, and some of the most widespread environmental contaminants are selectively toxic to dopaminergic neurons. Pesticides have long been connected to PD incidence, however, it has become increasingly apparent that other industrial byproducts likely influence neurodegeneration. For example, organic solvents, which are used in chemical, machining, and dry-cleaning industries, are of growing concern, as decades of solvent use and their effluence into the environment has contaminated much of the world’s groundwater and soil. Like some pesticides, certain organic solvents, such as the chlorinated halocarbon trichloroethylene (TCE), are mitochondrial toxicants, which are collectively implicated in the pathogenesis of dopaminergic neurodegeneration. Recently, we hypothesized a possible gene-environment interaction may occur between environmental mitochondrial toxicants and the protein kinase LRRK2, mutations of which are the most common genetic cause of familial and sporadic PD. In addition, emerging data suggests that elevated wildtype LRRK2 kinase activity also contributes to the pathogenesis of idiopathic PD. To this end, we investigated whether chronic, systemic TCE exposure (200 mg/kg) in aged rats produced wildtype LRRK2 activation and influenced predegenerative dopaminergic dysfunction. Interestingly, we found that TCE not only induced LRRK2 kinase activity in the brain, but produced a significant dopaminergic lesion in the nigrostriatal tract, elevated oxidative stress, and caused endolysosomal dysfunction and protein accumulation (α-synuclein). Together, these data suggest that TCE-induced LRRK2 kinase activity contributed to the selective toxicity of dopaminergic neurons. We conclude that gene-environment interactions between certain industrial contaminants and LRRK2 likely influence PD risk.

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