Cholesterol and Multiple Sclerosis

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It is incredible that medications that lower cholesterol have been proposed for the treatment of Multiple Sclerosis.  Myelin is 50% cholesterol and maintaining it requires huge amounts. No wonder statins  devastate the neural systems!

Here is a quote from our published paper on what you are not told cholesterol lowering treatments: (click text for full paper)

The process in which axons are protected by the myelin secretions of the oligodendrocyte requires a specialised cholesterol-rich membrane [42]. Klopfleisch et al. [43] describe experimental in vivo evidence that new myelin (re-myelination) secretion by oligodendrocytes is impaired by statins.  

Whilst they attribute much of this failure to signalling interference, they also prevented detrimental outcomes in vitro by re-incubating oligodendrocytes with cholesterol. How long are oligodendrocytes able to repair and maintain myelin in an environment where cholesterol is depleted?  

It has been argued that statins can prevent de-myelination [44] through a pleiotropic anti-inflammatory effect and this has led to research on its use as a multiple sclerosis therapy.  

This would appear to contradict Klopfleisch’s findings [43], until you consider that initially there may be multiple conflicting effects over different time scales: Possibly the initial inhibiting of an auto-immune action associated with a de-myelination and  subsequent inhibition of oligodendrocyte repairs by cholesterol depletion.

Research is needed to establish whether the apparent initial slowing of de-myelination in statin therapy would be followed by a catastrophic failure of the re-myelination work of oligodendrocyte exocytosis [45] as cholesterol synthesis fails. Furthermore, consideration should be given to the structural state of membranes involved in any auto-immune process where a complex interplay of essential membrane lipids, mediated by cholesterol, affects the immune response [46].

[42] Fitzner D, Schneider A, Kippert A, et al. Myelin basic protein-dependent plasma membrane reorganization in the formation of myelin EMBO J 2006; 25: 5037-48.

[43] Klopfleisch S, Merkler D, Schmitz M, et al. Negative impact of statins on oligodendrocytes and myelin formation in vitro and in vivo J Neurosci 2008; 28: 13609-14.

[44] Paintlia AS, Paintlia MK, Singh AK, Singh I. Inhibition of rho family functions by lovastatin promotes myelin repair in ameliorating experimental autoimmune encephalomyelitis Mol Pharmacol 2008; 73: 1381-93.

[45] Trajkovic K, Dhaunchak AS, Goncalves JT, et al. Neuron to glia signaling triggers myelin membrane exocytosis from endosomal storage sites J Cell Biol 2006; 172: 937-48.

[46] Harbige LS. Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3. Lipids 2003; 38: 323-41.

Cholesterol and Multiple Sclerosis

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