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Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death


Sierra, Saleta, Ramos, Maria C., Molina, Pilar, Esteo, Cynthia, Vázquez, Jose Antonio, Burgos, Javier S.


Journal Of Alzheimer's Disease: JAD, Volume: 23, No.: 2, Pages.: 307-318

Year of Publication



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.;


brain, cell death, cell line, cells cultured, cholesterol, cognitive, decline, drug effects, humans, metabolism, neurons, neuroprotective agents, pharmacology, phosphorylation, physiology, prevent, statins, tau proteins, to, unclear

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study


Type of Interventions

Risk Factor Modification

Risk Factor Modifications

General population health promotion

Pharmaceutical Interventions