Lovastatin induces the formation of abnormal myelin-like membrane sheets in primary oligodendrocytes.

摘要: Statins, well-known inhibitors of cholesterol synthesis and protein isoprenylation, have been proposed as therapeutic drugs for multiple sclerosis (MS). As lovastatin simvastatin, which are currently tested their use in MS, can cross the blood-brain barrier, they may affect cellular processes central nervous system. This is especially relevant with respect to remyelination a additional treatment because major component myelin. Here, we show that primary oligodendrocytes, treated lovastatin, form extensive membrane sheets, contain galactosphingolipids. However, these sheets devoid myelin proteins, basic (MBP) proteolipid (PLP). Reduced MBP expression was confirmed by SDS-PAGE Western blotting, situ hybridization experiments revealed blocks mRNA transport into oligodendrocyte processes. In contrast, PLP only mildly affected lovastatin. resulted intracellular accumulation prevented its translocation cell surface. Interestingly, another inhibitor (ro48-8071), does not interfere had similar effect on localization PLP, but it did localization. These results suggest affects predominantly inhibition synthesis, whereas reduced caused impaired isoprenylation. Based recommend carefully monitor statins myelination prior demyelinating diseases. (C) 2008 Wiley-Liss, Inc.