Pesticides, microglial NOX2, and Parkinson's disease.
Accumulating evidence indicates that pesticide exposure is associated with an increased risk for developing Parkinson's disease (PD). Several pesticides known to damage dopaminergic (DA) neurons, such as paraquat, rotenone, lindane, and dieldrin also demonstrate the ability to activate microglia, the resident innate immune cell in the brain. While each of these environmental toxicants may impact microglia through unique mechanisms, they all appear to converge on a common final pathway of microglial activation: NADPH oxidase 2 (NOX2) activation. This review will detail the role of microglia in selective DA neurotoxicity, highlight what is currently known about the mechanism of microglial NOX2 activation in these key pesticides, and describe the importance for DA neuron survival and PD etiology.
Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Campus, Richmond, VA 23298, USA.
Thomas
T
Taetzsch
Michelle L
ML
Block
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism*; D017628:Microglia / Q000201:enzymology* / Q000473:pathology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D010575:Pesticides / Q000633:toxicity*
D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010575:Pesticides; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases