Signaling Pathways Involved in 1-Octen-3-ol-Mediated Neurotoxicity in Drosophila melanogaster: Implication in Parkinson's Disease.

TitleSignaling Pathways Involved in 1-Octen-3-ol-Mediated Neurotoxicity in Drosophila melanogaster: Implication in Parkinson's Disease.
Publication TypeJournal Article
Year of Publication2013
AuthorsInamdar AA, Masurekar P, Hossain M, Richardson JR, Bennett JW
JournalNeurotoxicity research
Date Published2013 Aug 20
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.

DOI10.1039/c3cc44336a
Alternate JournalNeurotox Res