Environmental exposure to metals, including manganese, is an important risk factor for the development of parkinsonism (PS) in workers of welding or related industries. However, the relevance of metal-mediated PS to idiopathic Parkinson's disease (iPD) remains to be characterized. Clinically, differential diagnosis between metal-related PS and iPD is difficult, even in the best hands. This proposal is focused on discovering plasma biochemical markers unique to welders for differential diagnosis of various PS, monitoring PS progression, and identification of the population at risk for developing disabling PS. The techniques to be utilized are state-of-the-art proteomics that are actively employed currently in our laboratory in revealing biomarkers specific to iPD in both human brain tissue and cerebrospinal fluid (CSF).
Three specific aims are designed for the current proposal: 1) to differentiate PS in the plasma samples of welders from those of iPD using brain/CSF specific markers identified in iPD patients, 2) to develop plasma biomarkers unique to PS progression as well as early stages in welders using targeted and nonbiased quantitative proteomics, and 3) to confirm and validate PS plasma biomarkers in welders, which is a key process of biomarker discovery. The significance of this investigation includes: 1) identification of markers unique to PS, both in symptomatic welders and those at risk for developing PS, will help diagnose and monitor these patients as well as make it possible to remove the subjects at risk from the environment, thereby preventing them from developing PS;2) identification of protein markers unique to PS secondary to metal exposure likely suggests novel pathogenesis and therapeutic targets for the disease process;and 3) PS markers, if identified, can be widely utilized, given that plasma-based assays can be readily implemented in a clinical setting, even in developing countries or in remote areas of developed countries.

Public Health Relevance

Parkinsonism (PS) secondary to metal exposure is an incredibly important medical legal issue. Biochemical markers unique to early stages of PS may make it possible to remove the subjects at risk from the environment, thereby preventing them from developing disabling parkinsonism in later years.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES004696-25
Application #
8377591
Study Section
Special Emphasis Panel (ZES1-LKB-D)
Project Start
2012-04-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
25
Fiscal Year
2012
Total Cost
$315,329
Indirect Cost
$106,715
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Meador, James P; Yeh, Andrew; Gallagher, Evan P (2017) Determining potential adverse effects in marine fish exposed to pharmaceuticals and personal care products with the fish plasma model and whole-body tissue concentrations. Environ Pollut 230:1018-1029
Chang, Yu-Chi; Cole, Toby B; Costa, Lucio G (2017) Behavioral Phenotyping for Autism Spectrum Disorders in Mice. Curr Protoc Toxicol 72:11.22.1-11.22.21
Roqué, Pamela J; Costa, Lucio G (2017) Co-Culture of Neurons and Microglia. Curr Protoc Toxicol 74:11.24.1-11.24.17
Wang, Hao; Engstrom, Anna K; Xia, Zhengui (2017) Cadmium impairs the survival and proliferation of cultured adult subventricular neural stem cells through activation of the JNK and p38 MAP kinases. Toxicology 380:30-37
Yeh, Andrew; Marcinek, David J; Meador, James P et al. (2017) Effect of contaminants of emerging concern on liver mitochondrial function in Chinook salmon. Aquat Toxicol 190:21-31
Mills, Margaret G; Gallagher, Evan P (2017) A targeted gene expression platform allows for rapid analysis of chemical-induced antioxidant mRNA expression in zebrafish larvae. PLoS One 12:e0171025
Costa, Lucio G; Cole, Toby B; Coburn, Jacki et al. (2017) Neurotoxicity of traffic-related air pollution. Neurotoxicology 59:133-139
Costa, Lucio G; Cole, Toby B; Garrick, Jacqueline M et al. (2017) Metals and Paraoxonases. Adv Neurobiol 18:85-111
Al-Lozi, Amal; Nielsen, Susan Searles; Hershey, Tamara et al. (2017) Cognitive control dysfunction in workers exposed to manganese-containing welding fume. Am J Ind Med 60:181-188
Criswell, Susan R; Nielsen, Susan Searles; Warden, Mark et al. (2017) [18F]FDOPA positron emission tomography in manganese-exposed workers. Neurotoxicology :

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