Environment, Mitochondria, and Parkinson's Disease

@article{Sherer2002EnvironmentMA,
  title={Environment, Mitochondria, and Parkinson's Disease},
  author={Todd Sherer and Ranjita Betarbet and J. Timothy Greenamyre},
  journal={The Neuroscientist},
  year={2002},
  volume={8},
  pages={192 - 197}
}
Parkinson's disease (PD) is a common and disabling neurodegenerative disease marked by progressive motor dysfunction, which results from selective degeneration of the nigrostriatal pathway. Epidemiological studies indicate that exposure to pesticides, rural living, farming, and drinking well water are associated with an increased risk of developing PD. Rare cases of PD are caused by mutations in nuclear genes, and there is increasing evidence for susceptibility genes that alter disease risk… 

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References

SHOWING 1-10 OF 48 REFERENCES
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
TLDR
It is reported that chronic, systemic inhibition of complex I by the lipophilic pesticide, rotenone, causes highly selective nigrostriatal dopaminergic degeneration that is associated behaviorally with hypokinesia and rigidity.
Human complex I defects in neurodegenerative diseases.
  • A. Schapira
  • Biology, Medicine
    Biochimica et biophysica acta
  • 1998
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
TLDR
A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Abnormalities of the electron transport chain in idiopathic parkinson's disease
TLDR
It is hypothesized that the complex I abnormality may have an etiological role in the pathogenesis of Parkinson's disease and that this defect may be derived via the mitochondrial genome.
Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.
TLDR
A mutation was identified in the alpha-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease
TLDR
Results support the proposition that an mtDNA abnormality may underlie the mitochondrial defect in at least a proportion of PD patients and use of a mtDNA‐less (μo) cell line to determine if the complex I deficiency follows the genomic transplantation of platelet mtDNA.
A Generalised Increase in Protein Carbonyls in the Brain in Parkinson's but Not Incidental Lewy Body Disease
TLDR
The data show that either oxidative protein damage occurs widely but late in PD brain, and/or that l‐DOPA treatment contributes to protein oxidation.
Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions.
TLDR
The selective and specific nitration of alpha-synuclein in these disorders provides evidence to directly link oxidative and nitrative damage to the onset and progression of neurodegenerative synucleinopathies.
...
...