| Literature DB >> 24599114 |
Lluís Pujadas1, Daniela Rossi2, Rosa Andrés3, Cátia M Teixeira3, Bernat Serra-Vidal4, Antoni Parcerisas5, Rafael Maldonado6, Ernest Giralt7, Natàlia Carulla4, Eduardo Soriano8.
Abstract
Reelin is an extracellular matrix protein that is crucial for neural development and adult brain plasticity. While the Reelin signalling cascade has been reported to be associated with Alzheimer's disease (AD), the role of Reelin in this pathology is not understood. Here we use an in vitro approach to show that Reelin interacts with amyloid-β (Aβ42) soluble species, delays Aβ42 fibril formation and is recruited into amyloid fibrils. Furthermore, Reelin protects against both the neuronal death and dendritic spine loss induced by Aβ42 oligomers. In mice carrying the APP(Swe/Ind) mutation (J20 mice), Reelin overexpression delays amyloid plaque formation and rescues the recognition memory deficits. Our results indicate that by interacting with Aβ42 soluble species, delaying Aβ plaque formation, protecting against neuronal death and dendritic spine loss and preventing AD cognitive deficits, the Reelin pathway deserves consideration as a therapeutic target for the treatment of AD pathogenesis.Entities:
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Year: 2014 PMID： 24599114 DOI： 10.1038/ncomms4443
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919