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Biological Chemistry

Natural Product Looks Good For Alzheimer’s Drug

ACS Meeting News: Epothilone D improves cognition, reduces tau protein aggregates

by Lauren K. Wolf
April 2, 2012 | A version of this story appeared in Volume 90, Issue 14

The natural product epothilone D has taken another step down the long road toward becoming a treatment for Alzhei­mer’s disease, according to a new study (J. Neurosci., DOI: 10.1523/jneuro​sci.4922-11.2012). University of Pennsylvania researchers led by Kurt R. Brunden administered the compound for three months to mice with tau protein already aggregated in their brains. The drug improved the aged rodents’ cognition and nerve-cell integrity and, surprisingly, reduced tau aggregates in their brains. Tau protein normally stabilizes microtubules, the railroad tracks in nerve cells responsible for transporting cargo such as neurotransmitters. In Alzheimer’s patients, however, tau misfolds and aggregates, causing the microtubules to malfunction. Amos B. Smith III, the member of the research team who presented the work in San Diego, explained that rather than targeting tau, epothilone D stabilizes microtubules. A 2010 study of young mice by the same Penn team showed that the compound slows down the tau-related effects of Alzheimer’s (J. Neurosci., DOI: 10.1523/jneurosci.3059-10.2010). But that was a “prophylactic” study, Smith said. The new work, he explained, looked at the drug’s effects after the disease had developed “full bore.”

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