RT Journal Article SR Electronic T1 In Vitro Neurotoxicity of Methylisothiazolinone, a Commonly Used Industrial and Household Biocide, Proceeds via a Zinc and Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase-Dependent Pathway JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 7408 OP 7416 DO 10.1523/JNEUROSCI.22-17-07408.2002 VO 22 IS 17 A1 Du, Shen A1 McLaughlin, BethAnn A1 Pal, Sumon A1 Aizenman, Elias YR 2002 UL http://www.jneurosci.org/content/22/17/7408.abstract AB Neurodegenerative disorders in humans may be triggered or exacerbated by exposure to occupational or environmental agents. Here, we show that a brief exposure to methylisothiazolinone, a widely used industrial and household biocide, is highly toxic to cultured neurons but not to glia. We also show that the toxic actions of this biocide are zinc dependent and require the activation of p44/42 extracellular signal-regulated kinase (ERK) via a 12-lipoxygenase-mediated pathway. The cell death process also involves activation of NADPH oxidase, generation of reactive oxygen species, DNA damage, and overactivation of poly(ADP-ribose) polymerase, all occurring downstream from ERK phosphorylation. The toxic effects of methylisothiazolinone and related biocides on neurons have not been reported previously. Because of their widespread use, the neurotoxic consequences of both acute and chronic human exposure to these toxins need to be evaluated.