title: Signaling pathways involved in 1-octen-3-ol-mediated neurotoxicity in Drosophila melanogaster: implication in Parkinson’s disease.
abstract: Previously, we have pioneered Drosophila melanogaster as a reductionist model to show that 1-octen-3-ol, a musty-smelling volatile compound emitted by fungi and other organisms, causes loss of dopaminergic neurons and Parkinson’s disease-like symptoms in flies. Using our in vivo Drosophila system, the modulatory roles of important signaling pathways—JNK, Akt and the caspase-3-dependent apoptotic pathway were investigated in the context of 1-octen-3-ol-induced dopamine neurotoxicity. When heterozygous flies carrying mutant alleles for these proteins were exposed to 0.5 ppm of 1-octen-3-ol, they had shorter survival times than wild-type Drosophila. The overexpressed levels of wild-type JNK and Akt, (UAS-bsk and UAS-Akt) with TH-GAL4 and elav-GAL4 drivers improved the survival duration of exposed flies compared with controls. Thus, we found that Akt and JNK both protect against loss of dopamine activity associated with 1-octen-3-ol exposure, indicating the pro-survival role of these signaling pathways. Further, 1-octen-3-ol exposure was associated with activation of caspase 3, a hallmark for apoptosis.
authors: Arati A
authors: AA
authors: Inamdar
authors: Prakash
authors: P
authors: Masurekar
authors: Muhammad
authors: M
authors: Hossain
authors: Jason R
authors: JR
authors: Richardson
authors: Joan W
authors: JW
authors: Bennett
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D004331:Drosophila melanogaster; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D000442:Octanols / Q000633:toxicity*; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000442:Octanols; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; C038844:1-octen-3-ol
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