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Medline ® Abstract for Reference 47

of '1型神经纤维瘤病的管理和预后'

47
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The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1.
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Li W, Cui Y, Kushner SA, Brown RA, Jentsch JD, Frankland PW, Cannon TD, Silva AJ
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Curr Biol. 2005;15(21):1961.
 
Neurofibromatosis Type 1 (NF1) is a common neurological disorder caused by mutations in the gene encoding Neurofibromin, a p21Ras GTPase Activating Protein (GAP). Importantly, NF1 causes learning disabilities and attention deficits. A previous study showed that the learning and memory deficits of a mouse model of NF1 (nf1+/-) appear to be caused by excessive p21Ras activity leading to impairments in long-term potentiation (LTP), a cellular mechanism of learning and memory. Here, we identify lovastatin as a potent inhibitor of p21Ras/Mitogen Activated Protein Kinase (MAPK) activity in the brain. Lovastatin is a specific inhibitor of three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, used commonly for the treatment of hypercholesterolemia. We report that lovastatin decreased the enhanced brain p21Ras-MAPK activity of the nf1+/- mice, rescued their LTP deficits, and reversed their spatial learning and attention impairments. Therefore, these results demonstrate that lovastatin may prove useful in the treatment of Neurofibromatosis Type 1.
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Department of Neurobiology, University of California, Los Angeles, Los Angeles, California 90095, USA.
PMID