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Title: | A common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob disease |
Author: | Calero, Olga Bullido, María Jesús Clarimón, Jordi Frank García, Ana Martínez Martín, Pablo Lleó Bisa, Alberto Rey, María Jesús Sastre, Isabel Rábano, Alberto Pedro Cuesta, Jesús de Ferrer, Isidro (Ferrer Abizanda) Calero, Miguel |
Keywords: | Malalties per prions Metabolisme de proteïnes Trastorns del metabolisme Malaltia d'Alzheimer Malaltia de Creutzfeldt-Jakob Prion diseases Protein metabolism Disorders of metabolism Alzheimer's disease Creutzfeldt-Jakob disease |
Issue Date: | 30-Aug-2012 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | The β site APP cleaving enzyme 1 (BACE1) is the rate-limiting β-secretase enzyme in the amyloidogenic processing of APP and Aβ formation, and therefore it has a prominent role in Alzheimer"s disease (AD) pathology. Recent evidence suggests that the prion protein (PrP) interacts directly with BACE1 regulating its β-secretase activity. Moreover, PrP has been proposed as the cellular receptor involved in the impairment of synaptic plasticity and toxicity caused by Aβ oligomers. Provided that common pathophysiologic mechanisms are shared by Alzheimer"s and Creutzfeldt-Jakob (CJD) diseases, we investigated for the first time to the best of our knowledge a possible association of a common synonymous BACE1 polymorphism (rs638405) with sporadic CJD (sCJD). Our results indicate that BACE1 C-allele is associated with an increased risk for developing sCJD, mainly in PRNP M129M homozygous subjects with early onset. These results extend the very short list of genes (other than PRNP) involved in the development of human prion diseases; and support the notion that similar to AD, in sCJD several loci may contribute with modest overall effects to disease risk. These findings underscore the interplay in both pathologies of APP, Aβ oligomers, ApoE, PrP and BACE1, and suggest that aging and perhaps vascular risk factors may modulate disease pathologies in part through these key players |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0043926 |
It is part of: | PLoS One, 2012, vol. 7, num. 8, p. 1-6 |
URI: | http://hdl.handle.net/2445/49184 |
Related resource: | http://dx.doi.org/10.1371/journal.pone.0043926 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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