Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 23, Issue 2, Pages 307-318Publisher
IOS PRESS
DOI: 10.3233/JAD-2010-101179
Keywords
Blood brain barrier; cholesterol; HMG-CoA reductase; in vitro; neuroprotection; okadaic acid; statins
Categories
Funding
- NEURON BPh
- Agencia de Innovacion y Desarrollo de Andalucia of the Junta de Andalucia
- CDTI of the Ministerio de Ciencia e Innovacion
- Torres Quevedo program
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There is growing evidence to support the hypothesis that statins may act as neuroprotectants in several neuropathological conditions, including Alzheimer's disease. The mechanisms for neuroprotection are only partially understood, however, and pleiotropic phenomena could be involved. We have made a comparative study of 9 statins (lovastatin, mevastatin, pravastatin, simvastatin, cerivastatin, atorvastatin, fluvastatin, pitavastatin, and rosuvastatin), analyzing several parameters that could be related to neuroprotection, such as chemical structure, lipophilicity, potential blood-brain-barrier penetration (BBB), 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibition, cholesterol modulation in neurons, glia, and human hepatocyte cell lines, and protection against neurodegeneration caused by tau hyperphosphorylation induced by okadaic acid. Our results indicate that monacolin J derivatives (natural and semi-synthetic statins) are the best candidates for the prevention of neurodegenerative conditions due to their higher potential BBB penetration capacity, cholesterol lowering effect on neurons with a satisfactory safety profile, and in vitro protection against cell death caused by okadaic acid in culture. Among the nine statins studied, simvastatin presented the best characteristics for preventing neurodegenerative conditions.
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