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The Journal of Neuroscience, December 10, 2008, 28(50):13609-13614; doi:10.1523/JNEUROSCI.2765-08.2008

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Brief Communications
Negative Impact of Statins on Oligodendrocytes and Myelin Formation In Vitro and In Vivo

Steve Klopfleisch,^1 * Doron Merkler,^2 * Matthias Schmitz,¹ Sabine Klöppner,¹ Mariann Schedensack,² Gunnar Jeserich,⁴ Hans H. Althaus,¹ and Wolfgang Brück^2,3

¹Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany, ²Department of Neuropathology, University Medical Centre, Georg August University, 37075 Göttingen, Germany, ³Institute for Multiple Sclerosis Research, Gemeinnützige Hertie-Stiftung and University Medical Centre Göttingen, 37073 Göttingen, Germany, and ⁴Department of Neurobiology, University of Osnabrück, 49076 Osnabrück, Germany

Correspondence should be addressed to Doron Merkler at the above address. Email: merkler{at}med.uni-goettingen.de

Statins are widely prescribed drugs in cardiovascular diseases. Recent studies also demonstrated anti-inflammatory and immunomodulatory properties of statins by modulating the activity of small GTPases. Statins are thus considered as potential therapeutic drug for the inflammatory demyelinating disease multiple sclerosis (MS). However, little is known about the effects of statins on myelin-forming oligodendrocytes. Here, we show that statins hamper process and myelin formation in vitro by interfering with Ras and Rho signaling in mature oligodendrocytes and provide evidence that statins impair ongoing remyelination in vivo. Our findings may have significant implications for the application of statins in MS patients and in other demyelinating diseases of the CNS.

Key words: remyelination; multiple sclerosis; statins; cuprizone; oligodendrocytes; GTPases

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Received June 17, 2008; revised Oct. 24, 2008; accepted Nov. 5, 2008.

Correspondence should be addressed to Doron Merkler at the above address. Email: merkler{at}med.uni-goettingen.de

This article has been cited by other articles:

				V. E. Miron, S. P. Zehntner, T. Kuhlmann, S. K. Ludwin, T. Owens, T. E. Kennedy, B. J. Bedell, and J. P. Antel Statin Therapy Inhibits Remyelination in the Central Nervous System Am. J. Pathol., May 1, 2009; 174(5): 1880 - 1890. [Abstract] [Full Text] [PDF]

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