How do statins control neuroinflammation?

Statins are used widely to reduce the levels of low-density lipoproteins and cholesterol and thereby lower the incidence of atherosclerosis and cardiovascular disease. They achieve this through their ability to limit the production of mevalonate via blockade of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase. This enzyme is the rate limiting step controlling the de novo production of cholesterol. It is now clear from a number of studies in various animal models of neuroinflammation as well as in in vitro cell trafficking studies, that statins significantly attenuate both the clinical symptoms of neuroinflammation and the associated infiltration of inflammatory cells into the CNS. It has been known for some time that statins have additional effects, which appear independent of their cholesterol lowering action. Although the precise mechanism by which statins are able to exert this inhibitory effect on leukocyte infiltration and consequential neuroinflammatory disease is presently unclear, a number of potential mechanisms have been proposed.