Several independent, unrelated observations from humans, experimental animals and cell cultures led to the suggestion that cholesterol may play a pathogenic role in Alzheimer’s disease. This suggestion received support from retrospective data analysis revealing a reduced incidence of Alzheimer’s disease in hypercholesterolemic patients receiving statins, a family of cholesterol-lowering agents with a mechanism of action through inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase. However, the basis for such a beneficial effect remains unexplained. It seems unlikely that a reduction in serum LDL-cholesterol is responsible. These HMG-CoA reductase inhibitors, in addition to reducing cholesterol formation, also reduce the synthesis of isoprenoids, which are intermediates in the pathway for cholesterol biosynthesis. The activity of nitric oxide synthase is indirectly dependent on the prenylation of certain small molecular weight GTP-binding proteins. NO an intracellular signaling molecule can affect a variety of biological systems and may be responsible for the recognized pleiotropic effects of the statins. The beneficial effects in Alzheimer’s diseases may reflect such pleiotropicity.

Relationship between amyloid beta peptide, choesterol and statins

SORRENTINO, Giuseppe;
2004

Abstract

Several independent, unrelated observations from humans, experimental animals and cell cultures led to the suggestion that cholesterol may play a pathogenic role in Alzheimer’s disease. This suggestion received support from retrospective data analysis revealing a reduced incidence of Alzheimer’s disease in hypercholesterolemic patients receiving statins, a family of cholesterol-lowering agents with a mechanism of action through inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase. However, the basis for such a beneficial effect remains unexplained. It seems unlikely that a reduction in serum LDL-cholesterol is responsible. These HMG-CoA reductase inhibitors, in addition to reducing cholesterol formation, also reduce the synthesis of isoprenoids, which are intermediates in the pathway for cholesterol biosynthesis. The activity of nitric oxide synthase is indirectly dependent on the prenylation of certain small molecular weight GTP-binding proteins. NO an intracellular signaling molecule can affect a variety of biological systems and may be responsible for the recognized pleiotropic effects of the statins. The beneficial effects in Alzheimer’s diseases may reflect such pleiotropicity.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11367/16715
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