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Project Publications: University of Washington: Role of Paraoxonases (PONs) in Modulating Cadmium and Manganese Neurotoxicity

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Superfund Research Program

Role of Paraoxonases (PONs) in Modulating Cadmium and Manganese Neurotoxicity

Project Leader: Clement E. Furlong
Co-Investigators: Lucio G. Costa, Judit Marsillach Lopez
Grant Number: P42ES004696
Funding Period: 2009-2023
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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  • Costa LG. Central nervous system toxicity biomarkers. In: Biomarkers in Toxicology, Second Edition. Elsevier, New York, NY. pp.173-186.


  • Burdon J, Budnik LT, Baur X, Hageman G, Howard CV, Roig J, Coxon L, Furlong CE, Gee D, Loraine T, Terry AV, Midavaine J, Petersen H, Bron D, Soskolne CL, Michaelis S. 2023. Health consequences of exposure to aircraft contaminated air and fume events: a narrative review and medical protocol for the investigation of exposed aircrew and passengers. Environmental Health 22(1):43. doi:10.1186/s12940-023-00987-8 PMID:37194087 PMCID:PMC10186727
  • Doung RA, Garrick JM, Marsillach J. 2023. Advances in the use of residual newborn dried blood spots within environmental epidemiology. Curr Epidemiol Rep 10:264-274. doi:10.1007/s40471-023-00338-8
  • Garrick JM, Cole TB, Dao K, Phillips A, Costa LG. 2023. Perinatal diesel exhaust exposure causes persistent changes in the brains of aged mice: an assessment of behavioral and biochemical endpoints related to neurodegenerative disease. Environ Toxicol doi:10.1002/tox.23733 PMID:36629036



  • Costa LG, Aschner M, eds. 2021. Neurotoxicity of metals: Old issues and new developments
  • Garrick JM, Cole TB, Bammler TK, MacDonald JW, Marsillach J, Furlong CE, Costa LG. 2021. Paraoxonase 2 deficiency in mice alters motor behavior and causes region-specific transcript changes in the brain. Neurotoxicol Teratol 87(14):doi:10.1016/ PMID:34216730 PMCID:PMC8440460
  • Garrick JM, Costa LG, Cole TB, Marsillach J. 2021. Evaluating gait and locomotion in rodents with the CatWalk system. Curr Protoc 1(8):e220. doi:10.1002/cpz1.220 PMID:34370398 PMCID:PMC8363132
  • Marsillach J, Richter RJ, Costa LG, Furlong CE. 2021. Paraoxonase-1 (PON1) status analysis using non organophosphate substrates. Curr Protoc 1:e25. doi:10.1002/cpz1.25 PMID:33484495 PMCID:PMC7924808
  • Salazar JG, Marsillach J, Reverte I, Mackness B, Joven J, Camps J, Colomina MT. 2021. Paraoxonase-1 and -3 protein expression in brain of the Tg2576 mouse model of Alzheimer's disease. Antioxidants (Basel) 10(3):339. doi:10.3390/antiox10030339 PMID:33668379 PMCID:PMC7996151
  • Stingone JA, Triantafillou S, Larsen A, Kitt JP, Shaw GM, Marsillach J. 2021. Interdisciplinary data science to advance environmental health research and improve birth outcomes. Environ Res 197:doi:10.1016/j.envres.2021.111019 PMID:33737076 PMCID:PMC8187296
  • Zimetti F, Adorni MP, Marsillach J, Marchi C, Trentini A, Valacchi G, Cervellati C. 2021. Connection between the altered HDL antioxidant and anti-inflammatory properties and the risk to develop Alzheimer's disease: A narrative review. Oxid Med Cell Longev doi:10.1155/2021/6695796 PMID:33505588 PMCID:PMC7811424



  • Cervellati C, Valacchi G, Tisato V, Zuliani G, Marsillach J. 2019. Evaluating the link between Paraoxonase-1 levels and Alzheimer's disease development. Minerva Med 110(3):238-250. doi:10.23736/S0026-4806.18.05875-5 PMID:30334443
  • Chang Y, Daza R, Hevner R, Costa LG, Cole TB. 2019. Prenatal and early life diesel exhaust exposure disrupts cortical lamina organization: Evidence for a reelin-related pathogenic pathway induced by interleukin-6. Brain Behav Immun 78:105-115. doi:10.1016/j.bbi.2019.01.013 PMID:30668980 PMCID:PMC6557404





  • Burton C, Marsillach J, Zhang YS, Zhao W, Zheng X. 2015. Announcing our finalists. Bioanalysis 7(13):1667-1673. doi:10.4155/bio.15.90 PMID:26150248
  • Costa LG, Cole TB, Furlong CE. 2015. Paraoxonase (PON1) and Detoxication of Nerve Agents. Chapter 73 in: Handbook of Toxicology of Chemical Warfare Agents, 2nd edition. Academic Press,
  • Kim D, Burt AA, Ranchalis J, Vuletic S, Vaisar T, Li WF, Rosenthal EA, Dong W, Eintracht JF, Motulsky AG, Brunzell J, Albers JJ, Furlong CE, Jarvik GP. 2015. PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity. J Lipid Res 56(7):1351-1362. doi:10.1194/jlr.P058032 PMID:26009633 PMCID:PMC4479339
  • Krenz JE, Hofmann JN, Smith TR, Cunningham RN, Fenske RA, Simpson C, Keifer M. 2015. Determinants of butyrylcholinesterase inhibition among agricultural pesticide handlers in Washington State: an update. Ann Occup Hyg 59(1):25-40. doi:10.1093/annhyg/meu072 PMID:25261454 PMCID:PMC4290628
  • Marsillach J, Becker J, Vaisar T, Hahn B, Brunzell J, Furlong CE, de Boer I, McMahon M, Hoofnagle A. 2015. Paraoxonase-3 is depleted from the high-density lipoproteins of autoimmune disease patients with subclinical atherosclerosis. J Proteome Res 14(5):2046-2054. doi:10.1021/pr5011586 PMID:25723336 PMCID:PMC4434596


  • Cole TB, Li WF, Co AL, Hay AM, MacDonald JW, Bammler TK, Farin FM, Costa LG, Furlong CE. 2014. Repeated gestational exposure of mice to chlorpyrifos oxon is associated with paraoxonase 1 (PON1) modulated effects in maternal and fetal tissues. Toxicol Sci 141(2):409-422. doi:10.1093/toxsci/kfu144 PMID:25070982 PMCID:PMC4271046
  • Costa LG, de Laat R, Dao K, Pellacani C, Cole TB, Furlong CE. 2014. Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection. Neurotoxicology 43:3-9. doi:10.1016/j.neuro.2013.08.011 PMID:24012887 PMCID:PMC3942372
  • Costa LG, de Laat R, Tagliaferri S, Pellacani C. 2014. A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity. Toxicol Lett 230(2):282-294. doi:10.1016/j.toxlet.2013.11.011 PMID:24270005 PMCID:PMC4028440
  • Inoue S, Becker AL, Kim J, Shu Z, Soelberg SD, Weigel KM, Hiraiwa M, Cairns A, Lee H, Furlong CE, Oh K, Lee K, Gao D, Chung J, Cangelosi GA. 2014. Semi-automated, occupationally safe immunofluorescence microtip sensor for rapid detection of Mycobacterium cells in sputum. PLoS One 9(1):e86018. doi:10.1371/journal.pone.0086018 PMID:24465845 PMCID:PMC3899086
  • Kim D, Burt AA, Rosenthal EA, Ranchalis J, Eintracht JF, Hatsukami TS, Furlong CE, Marcovina S, Albers JJ, Jarvik GP. 2014. HDL-3 is a superior predictor of carotid artery disease in a case-control cohort of 1725 participants. J Am Heart Assoc 3(3):e000902. doi:10.1161/JAHA.114.000902 PMID:24965026 PMCID:PMC4309059
  • Kim D, Crosslin DR, Auer PL, Suzuki SM, Marsillach J, Burt AA, Gordon AS, Meschia JF, Nalls MA, Worrall BB, Longstreth WT, Gottesman RF, Furlong CE, Peters U, Rich SS, Nickerson DA, Jarvik GP. 2014. Rare coding variation in paraoxonase-1 is associated with ischemic stroke in the NHLBI Exome Sequencing Project. J Lipid Res 55(6):1173-1178. doi:10.1194/jlr.P049247 PMID:24711634 PMCID:PMC4031948
  • Marsillach J, Suzuki SM, Richter RJ, McDonald MG, Rademacher PM, MacCoss MJ, Hsieh EJ, Rettie AE, Furlong CE. 2014. Human valacyclovir hydrolase/biphenyl hydrolase-like protein is a highly efficient homocysteine thiolactonase. PLoS One 9(10):e110054. doi:10.1371/journal.pone.0110054 PMID:25333274 PMCID:PMC4198189
  • Strelitz J, Engel LS, Keifer M. 2014. Blood acetylcholinesterase and butyrylcholinesterase as biomarkers of cholinesterase depression among pesticide handlers. Occup Environ Med 71(12):842-847. doi:10.1136/oemed-2014-102315 PMID:25189163 PMCID:PMC4224972




  • Cole TB, Beyer RP, Bammler TK, Park SS, Farin FM, Costa LG, Furlong CE. 2011. Repeated developmental exposure of mice to chlorpyrifos oxon is associated with paraoxonase 1 (PON1)-modulated effects on cerebellar gene expression. Toxicol Sci 123:155-169. doi:10.1093/toxsci/kfr157 PMID:21673326 PMCID:PMC3164442
  • Costa LG, Furlong CE. 2011. Paraoxonase 1: Structure, Function and Polymorphisms. Chapter 7 in: Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology. Wiley, Hoboken, NJ. pp.85-96.
  • Costa LG, Giordano G, Furlong CE. 2011. Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: the hunt goes on. Biochem Pharmacol 81(3):337-344. doi:10.1016/j.bcp.2010.11.008 PMID:21093416 PMCID:PMC3077125
  • Giordano G, Cole TB, Furlong CE, Costa LG. 2011. Paraoxonase 2 (PON2) in the mouse central nervous system: a neuroprotective role?. Toxicol Appl Pharmacol 256:369-378. doi:10.1016/j.taap.2011.02.014 PMID:21354197 PMCID:PMC3155737
  • Kim JH, Stevens RC, MacCoss MJ, Goodlett DR, Scherl A, Richter RJ, Suzuki SM, Furlong CE, Marsillach J, Tomazela D, Schopfer LM, Lockridge O. 2011. Biomarkers of organophosphorus (OP) exposures in humans. Neurotoxicology 32:656-660. doi:10.1016/j.neuro.2011.06.005 PMID:21767566 PMCID:PMC3279568
  • Liyasova M, Li B, Schopfer LM, Nachon F, Masson P, Furlong CE, Lockridge O. 2011. Exposure to tri-o-cresyl phosphate detected in jet airplant passengers. Toxicol Appl Pharmacol 256:337-347. doi:10.1016/j.taap.2011.06.016 PMID:21723309 PMCID:PMC3205265


  • Cole TB, Park SS, Li WF, Furlong CE, Costa LG, Jansen KL. 2010. The toxicity of mixtures of specific organophosphorus (OP) compounds is modulated by paraoxonase 1 status. Advances in Experimental Medicine and Biology 660:47-60. doi:10.1007/978-1-60761-350-3_6 PMID:20221870 PMCID:PMC3035621
  • Furlong CE, Suzuki SM, Stevens RC, Marsillach J, Richter RJ, Jarvik GP, Checkoway H, Samii A, Costa LG, Griffith A, Roberts JW, Yearout D, Zabetian CP. 2010. Human PON1, a biomarker of risk of disease and exposure. Chem Biol Interact 187(1-3):355-361. doi:10.1016/j.cbi.2010.03.033 PMID:20338154 PMCID:PMC3035622
  • Hofmann JN, Keifer M, Checkoway H, De Roos AJ, Farin FM, Fenske RA, Richter RJ, van Belle G, Furlong CE. 2010. Biomarkers of sensitivity and exposure in Washington state pesticide handlers. Advances in Experimental Medicine and Biology 660:19-27. doi:10.1007/978-1-60761-350-3_3 PMID:20221867 PMCID:PMC3041670
  • Hofmann JN, Keifer M, De Roos AJ, Fenske RA, Furlong CE, van Belle G, Checkoway H. 2010. Occupational determinants of serum cholinesterase inhibition among organophosphate-exposed agricultural pesticide handlers in Washington State. Occup Environ Med 67(6):375-386. doi:10.1136/oem.2009.046391 PMID:19819864 PMCID:PMC2908529
  • Kim JH, Stevens RC, MacCoss MJ, Goodlett DR, Scherl A, Richter RJ, Suzuki SM, Furlong CE. 2010. Identification and characterization of biomarkers of organophosphorus (OP) exposures in humans. Advances in Experimental Medicine and Biology 660:61-71. doi:10.1007/978-1-60761-350-3_7 PMID:20221871 PMCID:PMC2878371
  • Richter RJ, Cole TB, Park SS, Otto TC, Cerasoli DM, Lenz DE, Furlong CE, Suzuki SM, Stevens RC. 2010. Engineering Human P0N1 in an E. coli Expression System. In: Paraoxonases in Inflammation, Infection and Toxicology. Humana Press, pp.37-46.
  • Richter RJ, Jarvik GP, Furlong CE. 2010. Paraoxonase 1 status as a risk factor for disease or exposure. Advances in Experimental Medicine and Biology 660:29-35. doi:10.1007/978-1-60761-350-3_4 PMID:20221868 PMCID:PMC2868909
  • Ross S, Brewin C, Curran H, Furlong CE, Abraham-Smith K, Harrison V. 2010. Neuropsychological and psychiatric functioning in sheep farmers exposed to low levels of organophosphate pesticides. Neurotoxicol Teratol 32(4):452-459. doi:10.1016/ PMID:20227490 PMCID:PMC3042861
  • Schopfer L, Furlong CE, Lockridge O. 2010. Development of diagnostics in the search for an explanation of aerotoxic syndrome. Anal Biochem 404(1):64-74. doi:10.1016/j.ab.2010.04.032 PMID:20447373 PMCID:PMC2900449
  • Suzuki SM, Stevens RC, Richter RJ, Cole TB, Park SS, Otto TC, Cerasoli DM, Lenz DE, Furlong CE. 2010. Engineering human PON1 in an E. coli expression system. Advances in Experimental Medicine and Biology 660:37-45. doi:10.1007/978-1-60761-350-3_5 PMID:20221869 PMCID:PMC3056878
  • Ticozzi N, LeClerc AL, Keagle PJ, Glass JD, Wills AM, van Blitterswijk M, Bosco DA, Rodriguez-Leyva I, Gellera C, Ratti A, Taroni F, McKenna-Yasek D, Sapp PC, Silvani V, Furlong CE, Brown RH, Landers JE. 2010. Paraoxonase gene mutations in amyotrophic lateral sclerosis. Ann Neurol 68(1):102-107. doi:10.1002/ana.21993 PMID:20582942 PMCID:PMC2945725



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