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Biological Chemistry

Steady Fix For Alzheimer's

Epothilone D could be useful for stabilizing the microtubules critical for transporting molecules in neurons

by Carmen Drahl
October 25, 2010 | A version of this story appeared in Volume 88, Issue 43

The natural product epothilone D is known for its anticancer properties, but a study now suggests it might also be useful for treating neurodegenerative ailments such as Alzheimer’s disease. One protein that goes awry in these brain diseases is tau, which stabilizes the microtubules critical for transporting molecules in neurons (C&EN, May 3, page 36). So some researchers are testing whether they can compensate for defective tau with microtubule-stabilizing molecules. Virginia M.-Y. Lee and John Q. Trojanowski’s team at the University of Pennsylvania School of Medicine had some success in this regard with the drug paclitaxel, but the molecule is not good at entering the brain. They then joined forces with Penn chemist Amos B. Smith III’s group, which in 2008 received an NIH grant to explore microtubule-stabilizing epothilones and other molecules. Together, they’ve found that epothilone D enters the brain and improves cognition in mice with diseased tau (J. Neurosci. 2010, 30, 13861). The researchers are now looking for other molecules that can do the job even better. Independent of the Penn team, Bristol-Myers Squibb filed for a patent in 2009 to use epothilone D for a similar strategy.


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