Linked Life Data

17344383

Source:http://linkedlifedata.com/resource/pubmed/id/17344383

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-3-8
pubmed:abstractText
Catastrophic loss of dopaminergic neurons is a hallmark of Parkinson's disease. Despite the recent identification of genes associated with familial parkinsonism, the etiology of most Parkinson's disease cases is not understood. Environmental toxins, such as the herbicide paraquat, appear to be risk factors, and it has been proposed that susceptibility is influenced by genetic background. The genetic model organism Drosophila is an advantageous system for the identification of genetic susceptibility factors. Genes that affect dopamine homeostasis are candidate susceptibility factors, because dopamine itself has been implicated in neuron damage. We find that paraquat can replicate a broad spectrum of parkinsonian behavioral symptoms in Drosophila that are associated with loss of specific subsets of dopaminergic neurons. In parallel with epidemiological studies that show an increased incidence of Parkinson's disease in males, male Drosophila exhibit paraquat symptoms earlier than females. We then tested the hypothesis that variation in dopamine-regulating genes, including those that regulate tetrahydrobiopterin, a requisite cofactor in dopamine synthesis, can alter susceptibility to paraquat-induced oxidative damage. Drosophila mutant strains that have increased or decreased dopamine and tetrahydrobiopterin production exhibit variation in susceptibility to paraquat. Surprisingly, protection against the neurotoxicity of paraquat is conferred by mutations that elevate dopamine pathway function, whereas mutations that diminish dopamine pools increase susceptibility. We also find that loss-of-function mutations in a negative regulator of dopamine production, Catecholamines-up, delay the onset of neurological symptoms, dopaminergic neuron death, and morbidity during paraquat exposure but confer sensitivity to hydrogen peroxide.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2457-67
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17344383-Animals, pubmed-meshheading:17344383-Biopterin, pubmed-meshheading:17344383-Catalase, pubmed-meshheading:17344383-Cell Aggregation, pubmed-meshheading:17344383-Disease Models, Animal, pubmed-meshheading:17344383-Dopamine, pubmed-meshheading:17344383-Drosophila, pubmed-meshheading:17344383-Drosophila Proteins, pubmed-meshheading:17344383-Dyskinesia, Drug-Induced, pubmed-meshheading:17344383-Female, pubmed-meshheading:17344383-Gene Expression Regulation, pubmed-meshheading:17344383-Genetic Predisposition to Disease, pubmed-meshheading:17344383-Hazardous Substances, pubmed-meshheading:17344383-Herbicides, pubmed-meshheading:17344383-Homeostasis, pubmed-meshheading:17344383-Longevity, pubmed-meshheading:17344383-Male, pubmed-meshheading:17344383-Mutation, pubmed-meshheading:17344383-Neurons, pubmed-meshheading:17344383-Paraquat, pubmed-meshheading:17344383-Parkinsonian Disorders
pubmed:year
2007
pubmed:articleTitle
Interaction of genetic and environmental factors in a Drosophila parkinsonism model.
pubmed:affiliation
Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama 35487-0344, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural