Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration.
Parkinson disease (PD) is the most common movement disorder and, although the exact causes are unknown, recent epidemiological and experimental studies indicate that several environmental agents may be significant risk factors. To date, these suspected environmental risk factors have been man-made chemicals. In this report, we demonstrate via genetic, biochemical, and immunological studies that the common volatile fungal semiochemical 1-octen-3-ol reduces dopamine levels and causes dopamine neuron degeneration in Drosophila melanogaster. Overexpression of the vesicular monoamine transporter (VMAT) rescued the dopamine toxicity and neurodegeneration, whereas mutations decreasing VMAT and tyrosine hydroxylase exacerbated toxicity. Furthermore, 1-octen-3-ol also inhibited uptake of dopamine in human cell lines expressing the human plasma membrane dopamine transporter (DAT) and human VMAT ortholog, VMAT2. These data demonstrate that 1-octen-3-ol exerts toxicity via disruption of dopamine homeostasis and may represent a naturally occurring environmental agent involved in parkinsonism.
Department of Plant Biology and Pathology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.
Arati A
AA
Inamdar
Muhammad M
MM
Hossain
Alison I
AI
Bernstein
Gary W
GW
Miller
Jason R
JR
Richardson
Joan Wennstrom
JW
Bennett
D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects*; D004330:Drosophila; D018613:Microscopy, Confocal; D009068:Movement / Q000187:drug effects; D009410:Nerve Degeneration / Q000139:chemically induced*; D000442:Octanols / Q000633:toxicity*; D010675:Pheromones / Q000633:toxicity*
D000442:Octanols; D010675:Pheromones; D004298:Dopamine; C038844:1-octen-3-ol
building-related illness; mold; mushroom alcohol