| Amphotericin B, identified from a natural product screen, antagonizes CNS inhibitors to promote axon growth via activation of an Akt pathway in neurons. | |
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MedLine Citation:
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PMID: 20345749 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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One of the major barriers to successful axon regeneration in the adult CNS is the presence of inhibitory molecules that originate from the myelin sheath and glial scar. So far, only a small number of pharmacological compounds have exhibited functional activity against CNS inhibitors in promoting axon regeneration after injury. To search for novel compounds that enhance neurite outgrowth in vitro, we initiated a screen of a collection of natural products. We identified four compounds with the potential to promote growth over a myelin substrate. Of these, Amphotericin B (AmB) was shown to enhance neurite outgrowth and antagonize activities of major myelin associated inhibitors and glial-scar-derived chondroitin sulfate proteoglycans. AmB was found to activate Akt and thereby suppress the activity of glycogen synthase kinase 3 beta. Also, a cell permeable peptide that inhibits Akt activity was shown to block the effect of AmB in promoting axonal growth, while another peptide that increases Akt activity stimulated axonal growth in the presence of the myelin associated inhibitors. Our results suggest that AmB can promote neurite outgrowth over a wide range of inhibitory substrates via a mechanism that involves activation of Akt. |
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Authors:
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Ying Gao; Kangwen Deng; Zixuan Cao; Edmund I Graziani; Adam M Gilbert; Frank E Koehn; Andrew Wood; Patrick Doherty; Frank S Walsh |
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Publication Detail:
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Type: Journal Article Date: 2010-03-25 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 113 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-22 Completed Date: 2010-07-08 Revised Date: 2010-07-28 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 1331-42 Citation Subset: IM |
Affiliation:
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Discovery Neuroscience, Pfizer Research, Princeton, New Jersey, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amphotericin B
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pharmacology* Animals Antifungal Agents / pharmacology* Axons / drug effects* Biological Products / pharmacology* Blotting, Western Cell Proliferation / drug effects Drug Evaluation, Preclinical Myelin-Associated Glycoprotein / antagonists & inhibitors, pharmacology Nerve Regeneration / drug effects Neurites / drug effects Neurons / drug effects* Oncogene Protein v-akt / metabolism* Principal Component Analysis Proteochondroitin Sulfates / antagonists & inhibitors, pharmacology Rats Signal Transduction / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Antifungal Agents; 0/Biological Products; 0/Myelin-Associated Glycoprotein; 0/Proteochondroitin Sulfates; 1397-89-3/Amphotericin B; EC 2.7.11.1/Oncogene Protein v-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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