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Review
. 2010 Sep;67(9):1062-7.
doi: 10.1001/archneurol.2010.199.

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in the treatment of central nervous system diseases

Joshua Z Willey  1 , Mitchell S V Elkind
Affiliations
Review

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in the treatment of central nervous system diseases

Joshua Z Willey et al. Arch Neurol. 2010 Sep.

Abstract

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are among the most prescribed medications in the United States. Statins act on the rate-limiting step in cholesterol biosynthesis (the conversion of HMG-CoA to mevalonate) and are effective in treating dyslipidemia. However, statins decrease other downstream products of the mevalonate pathway, and it is via these pathways that statins may affect inflammation, nitric oxide synthesis, the coagulation cascade, and other processes. Through these pleiotropic effects, statins may have an effect on neurologic diseases, including ischemic and hemorrhagic stroke, Alzheimer disease, Parkinson disease, and multiple sclerosis. This article reviews the basic biochemistry of statins as it relates to these pleiotropic effects, the potential role of statins in several neurologic disorders, and the results of clinical trials performed for several of these conditions.

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Figures

Figure
Figure
Summary of important biochemical pathways for statins and their reported mechanisms of action. Text boxes indicate potential mechanisms of action for the benefit of statins. eNOS indicates endothelial nitric oxide synthase; HMG-CoA, 3-hydroxy-3-methylglutaryl–coenzyme A; NMDA, N-methyl-d-aspartate; Rho GTPase, Rho family of guanosine triphosphatases; and tPA, tissue plasminogen activator.
See this image and copyright information in PMC

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