Abstract | OBJECTIVE: Peripheral neurotoxicity is a major dose-limiting side effect of many chemotherapeutic drugs. Currently there are no effective disease-modifying therapies for chemotherapy-induced peripheral neuropathies, but these side effects of chemotherapy are potentially ideal targets for development of neuroprotective therapies, because candidate drugs can be co- or preadministered before the injury to peripheral axons takes place. METHODS: We used a phenotypic drug screening approach to identify ethoxyquin as a potential neuroprotective drug and carried out additional biochemical experiments to identify its mechanism of action. RESULTS: INTERPRETATION:
Ethoxyquin and its novel derivatives as well as other classes of small molecules that act as Hsp90 modulators may offer a new opportunity for development of drugs to prevent chemotherapy-induced axonal degeneration.
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Authors | Jing Zhu, Weiran Chen, Ruifa Mi, Chunhua Zhou, Nicole Reed, Ahmet Höke |
Journal | Annals of neurology
(Ann Neurol)
Vol. 74
Issue 6
Pg. 893-904
(Dec 2013)
ISSN: 1531-8249 [Electronic] United States |
PMID | 23955554
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Validation Study)
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Copyright | © 2013 American Neurological Association. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- HSP90 Heat-Shock Proteins
- Neuroprotective Agents
- Ethoxyquin
- Paclitaxel
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(adverse effects)
- Axons
(drug effects)
- Cell Line
- Drug Evaluation, Preclinical
(methods)
- Ethoxyquin
(pharmacology)
- HSP90 Heat-Shock Proteins
(metabolism)
- Male
- Mice
- Nerve Degeneration
(chemically induced, drug therapy)
- Neurons
(drug effects)
- Neuroprotective Agents
(pharmacology)
- Neurotoxicity Syndromes
(drug therapy)
- Paclitaxel
(adverse effects, antagonists & inhibitors)
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