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Impact of HMG-CoA reductase inhibition on brain pathology

Item Type:Review
Title:Impact of HMG-CoA reductase inhibition on brain pathology
Creators Name:Zipp, F. and Waiczies, S. and Aktas, O. and Neuhaus, O. and Hemmer, B. and Schraven, B. and Nitsch, R. and Hartung, H.P.
Abstract:Over the past two decades, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (HMGCRIs), originally designed to lower cholesterol blood levels, have been found to affect GTPase signaling during normal intracellular tasks. This finding has prompted use of these drugs in pathological situations, where such signaling processes need to be manipulated. Here, we review recent progress on the outcome of modulating GTPase signaling after inhibition of protein prenylation by HMGCRIs. We also discuss current controversies over the direct implications of these cholesterol-lowering agents on cholesterol-rich membrane lipid rafts and associated signaling. By reviewing these two different cellular events and the evidence from clinical studies, an overall assessment can be made of the concept of interfering with the HMG-CoA reductase pathway in different brain pathologies. We thereby provide a rational link between the benefit of applying HMGCRIs in brain pathologies, such as multiple sclerosis, Alzheimers disease and stroke, and the impact on signaling in specific cell types crucial to disease pathogenesis.
Keywords:Alzheimer Disease, Anti-Inflammatory Agents, Brain, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Multiple Sclerosis, Signal Transduction, Stroke, Animals
Source:Trends in Pharmacological Sciences
Page Range:342-349
Date:July 2007
Additional Information:The original publication is available at www.sciencedirect.com
Official Publication:https://doi.org/10.1016/j.tips.2007.05.001
PubMed:View item in PubMed

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