Main > NEUROLOGY. > Alzheimer's Disease > Treatment > Cholesterol. Connection > HMG CoA Reductase Inh.>Statins > Org.: USA. C (Study) > NPLS Contents
Authors proffer an additional explanation for the beneficial effects of statins. Authors note that amyloid- deposition evokes an inflammatory response in the brain. In particular, amyloid- plaques prompt immune cells known as microglia and white blood cells called monocytes to release inflammation-promoting molecules such as interleukin-1, tumor necrosis factor , and reactive oxygen and nitrogen species. Exposure to these compounds contributes to the death of neurons.
When Authors dosed cultured microglial cells and monocytes with statins, they found that the drugs "robustly inhibit the amyloid--stimulated expression" of the proinflammatory compounds. Adding cholesterol to the culture can not reverse this suppression. The researchers interpret this evidence to mean that statins "anti-inflammatory actions are distinct from their cholesterol-lowering actions".
However, both statin effects can be traced to the drugs inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase. This rate-limiting enzyme controls an early step in the biosynthesis of cholesterol. Inhibiting the enzyme not only reduces production of cholesterol but also reduces production of a whole pile of intermediates that precede cholesterol.
Those intermediates include the isoprenoids, which can branch off into another pathway unrelated to cholesterol production. In this alternative pathway, isoprenoids activate members of the Rho family of small G proteins that are involved in inflammatory signaling. By reducing isoprenoid production, statins limit activation of this inflammatory pathway.
"The Org.: USA. T paper suggests that statins act in neurons through mechanisms similar to those described by us in microglia," Author explains. Furthermore, "statins and NSAIDs share a common general mechanism to alter Alzheimer s disease pathogenesis in which APP processing is downregulated in neurons and inflammatory responses are suppressed in microglia."
In their work, Authors focused on the cholesterol-independent activities of statins. But that doesn not mean the drugs effects on cholesterol are unimportant in the war against Alzheimer s. In fact, until the anti-inflammation connection was made, the reduced risk of Alzheimer s among statin users generally had been attributed solely to cholesterol reduction.
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