Small-molecule-mediated axonal branching in Caenorhabditis elegans - PubMed (original) (raw)
Small-molecule-mediated axonal branching in Caenorhabditis elegans
Katherine Zlotkowski et al. Chembiochem. 2013.
Abstract
An in vivo system for monitoring small-molecule-mediated neuronal branching has been developed by using C. elegans. Growth-promoting compounds can be detected by visual inspection of GFPlabeled cholinergic neurons, as axonal branching occurs following treatment with neurotrophic agents. Investigation of the structure-activity relationship of the neurotrophic natural product clovanemagnolol (1) led us to a comparable chemically edited derivative.
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Figures
Figure 1
Cholinergic branching in C. elegans. A), B) Normal morphology in the ventral and dorsal nerve cords and commissures. C), D) Lower level background branching observed in untreated control worms. E), F) Branching caused by the natural product clovanemagnolol (1). G), H) Complex branching in animals treated with caryolanemagnolol (2).
Figure 2
Representative outgrowth induced by small molecules. Nematodes treated with A) amphotericin B, B) trigonelline, C) dibutyryl-cAMP, D) carnosic acid, and E) garcinol.
Figure 3
A) Outgrowth reported for nematodes treated with 2 μM small molecules, with branching observed in ≥25% of nematodes. B) The structures of the active compounds identified above.
Scheme 1
One-step synthesis of clovanebisphenol from β-caryophyllene oxide. a) (PhO)2P(O)OH, CH2Cl2, 23°C, 16%.
References
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- Stanfield BB, Oleary DDM, Fricks C. Nature. 1982;298:371–373. -PubMed
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