Discussion
How strong is the association between pesticide exposure and increased risk for Parkinson's disease and how do we translate this association into therapeutic strategies?
Certain pesticides, including paraquat, rotenone and maneb, have been linked to increased risk for PD. How strong is this association and how does it compare to other known risk factors (such as genetic factors)? What is known about the mechanisms linking pesticide exposure to PD pathogenesis and can this knowledge be translated into actual therapeutic strategies?
Responses:
Agent Orange linked to ...
Investigating pesticide ...
Reference:
Costello S, Cockburn M, Bronstein J, Zhang X, Ritz B. Parkinson's disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. Am J Epidemiol. 2009;169(8):919-26.
Ritz BR, Manthripragada AD, Costello S, Lincoln SJ, Farrer MJ, Cockburn M, et al. Dopamine transporter genetic variants and pesticides in Parkinson's disease. Environ Health Perspect. 2009;117(6):964-9.
Kelada SN, Checkoway H, Kardia SL, Carlson CS, Costa-Mallen P, Eaton DL, et al. 5' and 3' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study. Hum Mol Genet. 2006;15(20):3055-62.
Gatto NM, Cockburn M, Bronstein J, Manthripragada AD, Ritz B. Well-water consumption and Parkinson's disease in rural California. Environ Health Perspect. 2009;117(12):1912-8.
Manthripragada AD, Costello S, Cockburn MG, Bronstein JM, Ritz B. Paraoxonase 1, agricultural organophosphate exposure, and Parkinson disease. Epidemiology. 2010;21(1):87-94.
Question for Dr. Ritz
Genes and Environment
Genes and Environment
Tackling Complexity
DOPAL provides a key ...
Reference:
Kristal BS, Conway AD, Brown AM, Jain JC, Ulluci PA, Li SW, et al. Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria. Free Radic Biol Med. 2001;30(8):924-31.
Burke WJ, Li S, Williams EA, Nonneman R, Zahm DS. 3,4-Dihydroxyphenylacetaldehyde is the toxic dopamine metabolite in vivo: implications for Parkinson's disease pathogenesis. Brain Res. 2003;989(2):205-13.
Marchitti SA, Deitrich RA, Vasiliou V. Neurotoxicity and metabolism of the catecholamine-derived 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde: the role of aldehyde dehydrogenase. Pharmacol Rev. 2007;59(2):125-50.
Lamensdorf I, Eisenhofer G, Harvey-White J, Nechustan A, Kirk K, Kopin IJ. 3,4-Dihydroxyphenylacetaldehyde potentiates the toxic effects of metabolic stress in PC12 cells. Brain Res. 2000;868(2):191-201.
Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci. 2000;3(12):1301-6.
McCormack AL, Atienza JG, Johnston LC, Andersen JK, Vu S, Di Monte DA. Role of oxidative stress in paraquat-induced dopaminergic cell degeneration. J Neurochem. 2005;93(4):1030-7.
Florang VR, Rees JN, Brogden NK, Anderson DG, Hurley TD, Doorn JA. Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal. Neurotoxicology. 2007;28(1):76-82.
Jinsmaa Y, Florang VR, Rees JN, Anderson DG, Strack S, Doorn JA. Products of oxidative stress inhibit aldehyde oxidation and reduction pathways in dopamine catabolism yielding elevated levels of a reactive intermediate. Chem Res Toxicol. 2009;22(5):835-41.
Norian LA, Kucaba TA, Earel JK, Knutson T, Vanoosten RL, Griffith TS. J Oncol. 2009;2009:408038.
