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Ascaroside Pheromones: Chemical Biology and Pleiotropic Neuronal Functions

1
Interdisciplinary Program in Integrative Omics for Biomedical Science, Yonsei University, Seoul 03722, Korea
2
Yonsei Proteome Research Center, Yonsei University, Seoul 03722, Korea
3
Department of Chemical Physiology and Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 3898; https://doi.org/10.3390/ijms20163898
Received: 12 July 2019 / Revised: 26 July 2019 / Accepted: 7 August 2019 / Published: 9 August 2019
(This article belongs to the Special Issue Natural Products and Neuroprotection)
Pheromones are neuronal signals that stimulate conspecific individuals to react to environmental stressors or stimuli. Research on the ascaroside (ascr) pheromones in Caenorhabditis elegans and other nematodes has made great progress since ascr#1 was first isolated and biochemically defined in 2005. In this review, we highlight the current research on the structural diversity, biosynthesis, and pleiotropic neuronal functions of ascr pheromones and their implications in animal physiology. Experimental evidence suggests that ascr biosynthesis starts with conjugation of ascarylose to very long-chain fatty acids that are then processed via peroxisomal β-oxidation to yield diverse ascr pheromones. We also discuss the concentration and stage-dependent pleiotropic neuronal functions of ascr pheromones. These functions include dauer induction, lifespan extension, repulsion, aggregation, mating, foraging and detoxification, among others. These roles are carried out in coordination with three G protein-coupled receptors that function as putative pheromone receptors: SRBC-64/66, SRG-36/37, and DAF-37/38. Pheromone sensing is transmitted in sensory neurons via DAF-16-regulated glutamatergic neurotransmitters. Neuronal peroxisomal fatty acid β-oxidation has important cell-autonomous functions in the regulation of neuroendocrine signaling, including neuroprotection. In the future, translation of our knowledge of nematode ascr pheromones to higher animals might be beneficial, as ascr#1 has some anti-inflammatory effects in mice. To this end, we propose the establishment of pheromics (pheromone omics) as a new subset of integrated disciplinary research area within chemical ecology for system-wide investigation of animal pheromones. View Full-Text
Keywords: ascaroside pheromone; C. elegans; dauer; neuronal signaling; sexual behavior; survival signals; stress response ascaroside pheromone; C. elegans; dauer; neuronal signaling; sexual behavior; survival signals; stress response
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Park, J.Y.; Joo, H.-J.; Park, S.; Paik, Y.-K. Ascaroside Pheromones: Chemical Biology and Pleiotropic Neuronal Functions. Int. J. Mol. Sci. 2019, 20, 3898.

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