Brunden KR, Zhang B, Carroll J, Yao Y, Potuzak JS, Hogan AM, Iba M, James MJ, Xie SX, Ballatore C, Smith AB, Lee VM, Trojanowski JQ. Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci. 2010 Oct 13;30(41):13861-6. PubMed.
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Cellzome AG
The authors demonstrate clear beneficial effects of low concentrations of epothilone D, a brain-permeable microtubule-stabilizing agent, on transgenic mice that develop forebrain tau inclusions. Similar approaches using the marketed cancer drug paclitaxel (Taxol) have been hampered by side effects due to the high doses needed to achieve efficacious drug levels in the brain. The data point to a promising therapeutic strategy of using brain-permeable MT drugs and strengthen the notion that microtubule function and axonal integrity is dependent on tau. It will be interesting to see whether epothilone D also shows efficacy in models of neurodegeneration that are not directly caused by a loss of tau function. If yes, this may bode well for related therapeutic approaches targeting microtubules, like the recent selective HDAC6 inhibitors, and for the approaches that target tau function, like inhibitors of tau kinases.
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