Negative impact of statins on oligodendrocytes and myelin formation in vitro and in vivo.
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.
Klopfleisch
Steve
S
Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
Merkler
Doron
D
Schmitz
Matthias
M
Klöppner
Sabine
S
Schedensack
Mariann
M
Jeserich
Gunnar
G
Althaus
Hans H
HH
Brück
Wolfgang
W
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine; D018631:ras Proteins / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000187:drug effects
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018631:ras Proteins; D020741:rho GTP-Binding Proteins