Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration

Arati A. Inamdar, Muhammad M. Hossain, Alison I. Bernstein, Gary W. Miller, Jason R. Richardson, Joan Wennstrom Bennett

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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 VMATand 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.

Original languageEnglish (US)
Pages (from-to)19561-19566
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number48
DOIs
StatePublished - Nov 26 2013

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Building-related illness
  • Mold
  • Mushroom alcohol

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