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dc.contributor.authorCarro, Eva-
dc.contributor.authorSpuch, Carlos-
dc.contributor.authorTrejo, José L.-
dc.contributor.authorAntequera, D.-
dc.contributor.authorTorres Alemán, Ignacio-
dc.date.accessioned2012-11-21T15:51:33Z-
dc.date.available2012-11-21T15:51:33Z-
dc.date.issued2005-
dc.identifierdoi: 10.1523/JNEUROSCI.2909-05.2005-
dc.identifierissn: 0270-6474-
dc.identifier.citationJournal of Neuroscience 25: 10884- 10893 (2005)-
dc.identifier.urihttp://hdl.handle.net/10261/60810-
dc.description.abstractThe involvement of circulating insulin-like growth factor I (IGF-I) in the beneficial effects of physical exercise on the brain makes this abundant serum growth factor a physiologically relevant neuroprotective signal. However, the mechanisms underlying neuroprotection by serum IGF-I remain primarily unknown. Among many other neuroprotective actions, IGF-I enhances clearance of brain amyloid β (Aβ) by modulating transport/production of Aβ carriers at the blood-brain interface in the choroid plexus. We found that physical exercise increases the levels of the choroid plexus endocytic receptor megalin/low-density lipoprotein receptor-related protein-2 (LRP2), a multicargo transporter known to participate in brain uptake of Aβ carriers. By manipulating choroid plexus megalin levels through viral-directed overexpression and RNA interference, we observed that megalin mediates IGF-I-induced clearance of Aβ and is involved in IGF-I transport into the brain. Through this dual role, megalin participates in the neuroprotective actions of IGF-I including prevention of tau hyperphosphorylation and maintenance of cognitive function in a variety of animal models of cognitive loss. Because we found that in normal aged animals, choroid plexus megalin/LRP2 is decreased, an attenuated IGF-I/megalin input may contribute to increased risk of neurodegeneration, including late-onset Alzheimer's disease. Copyright © 2005 Society for Neuroscience.-
dc.language.isoeng-
dc.publisherSociety for Neuroscience-
dc.rightsclosedAccess-
dc.titleChoroid plexus megalin is involved in neuroprotection by serum insulin-like growth factor I-
dc.typeartículo-
dc.identifier.doi10.1523/JNEUROSCI.2909-05.2005-
dc.date.updated2012-11-21T15:51:33Z-
dc.description.versionPeer Reviewed-
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