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Title: Signaling pathways involved in 1-octen-3-ol-mediated neurotoxicity in Drosophila melanogaster: implication in Parkinson’s disease.

Authors: Inamdar, Arati A; Masurekar, Prakash; Hossain, Muhammad; Richardson, Jason R; Bennett, Joan W

Published In Neurotox Res, (2014 Feb)

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.

PubMed ID: 23959949 Exiting the NIEHS site

MeSH Terms: Animals; Caspase 3/drug effects; Caspase 3/metabolism*; Disease Models, Animal; Dopaminergic Neurons/drug effects; Dopaminergic Neurons/metabolism*; Drosophila melanogaster; MAP Kinase Signaling System/drug effects; MAP Kinase Signaling System/physiology*; Octanols/toxicity*; Parkinson Disease/enzymology; Parkinson Disease/metabolism*; Proto-Oncogene Proteins c-akt/drug effects; Proto-Oncogene Proteins c-akt/metabolism*

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