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Proc Natl Acad Sci U S A

Title:		Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration
Author(s):		Inamdar AA; Hossain MM; Bernstein AI; Miller GW; Richardson JR; Bennett JW;
Address:		"Department of Plant Biology and Pathology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901"
Journal Title:		Proc Natl Acad Sci U S A
Year:		2013
Volume:		20131111
Issue:		48
Page Number:		19561 - 19566
DOI:		10.1073/pnas.1318830110
ISSN/ISBN:		1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking)
Abstract:		"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"
Keywords:		"Analysis of Variance Animals Chromatography, High Pressure Liquid Dopamine/*metabolism Dopaminergic Neurons/*drug effects Drosophila Microscopy, Confocal Movement/drug effects Nerve Degeneration/*chemically induced Octanols/*toxicity Pheromones/*toxicity;"
Notes:		"MedlineInamdar, Arati A Hossain, Muhammad M Bernstein, Alison I Miller, Gary W Richardson, Jason R Bennett, Joan Wennstrom eng P30ES019776/ES/NIEHS NIH HHS/ R01ES015991/ES/NIEHS NIH HHS/ P30 ES019776/ES/NIEHS NIH HHS/ R21NS072097/NS/NINDS NIH HHS/ U01 NS079249/NS/NINDS NIH HHS/ T32 ES012870/ES/NIEHS NIH HHS/ R21 NS072097/NS/NINDS NIH HHS/ P50NS071669/NS/NINDS NIH HHS/ P30 ES005022/ES/NIEHS NIH HHS/ R01 ES015991/ES/NIEHS NIH HHS/ P50 NS071669/NS/NINDS NIH HHS/ P30ES005022/ES/NIEHS NIH HHS/ Research Support, N.I.H., Extramural 2013/11/13 Proc Natl Acad Sci U S A. 2013 Nov 26; 110(48):19561-6. doi: 10.1073/pnas.1318830110. Epub 2013 Nov 11"