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dc.contributor.author | Rostagno, Agueda | |
dc.contributor.author | Calero, Miguel | |
dc.contributor.author | Holton, Janice L | |
dc.contributor.author | Revesz, Tamas | |
dc.contributor.author | Lashley, Tammaryn | |
dc.contributor.author | Ghiso, Jorge | |
dc.date.accessioned | 2022-04-25T12:06:31Z | |
dc.date.available | 2022-04-25T12:06:31Z | |
dc.date.issued | 2021-07-21 | |
dc.identifier.citation | Neurobiol Dis. 2021;158:105452. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/14167 | |
dc.description.abstract | Familial British and Danish dementias (FBD and FDD) share striking neuropathological similarities with Alzheimer's disease (AD), including intraneuronal neurofibrillary tangles as well as parenchymal and vascular amyloid deposits. Multiple amyloid associated proteins with still controversial role in amyloidogenesis colocalize with the structurally different amyloid peptides ABri in FBD, ADan in FDD, and Aβ in AD. Genetic variants and plasma levels of one of these associated proteins, clusterin, have been identified as risk factors for AD. Clusterin is known to bind soluble Aβ in biological fluids, facilitate its brain clearance, and prevent its aggregation. The current work identifies clusterin as the major ABri- and ADan-binding protein and provides insight into the biochemical mechanisms leading to the association of clusterin with ABri and ADan deposits. Mirroring findings in AD, the studies corroborate clusterin co-localization with cerebral parenchymal and vascular amyloid deposits in both disorders. Ligand affinity chromatography with downstream Western blot and amino acid sequence analyses unequivocally identified clusterin as the major ABri- and ADan-binding plasma protein. ELISA highlighted a specific saturable binding of clusterin to ABri and ADan with low nanomolar Kd values within the same range as those previously demonstrated for the clusterin-Aβ interaction. Consistent with its chaperone activity, thioflavin T binding assays clearly showed a modulatory effect of clusterin on ABri and ADan aggregation/fibrillization properties. Our findings, together with the known multifunctional activity of clusterin and its modulatory activity on the complex cellular pathways leading to oxidative stress, mitochondrial dysfunction, and the induction of cell death mechanisms - all known pathogenic features of these protein folding disorders - suggests the likelihood of a more complex role and a translational potential for the apolipoprotein in the amelioration/prevention of these pathogenic mechanisms. | es_ES |
dc.description.sponsorship | This work was supported by grants from the National Institutes of Health NS051715 (to AR) and AG030539, AG051266, AG059695, and AG065651 (to JG) and from CIBERNED and the Spanish Ministry of Science (SAF2016-78603-R and PID2019-110401RB-I00) and Institutional grants from the Queen Sofia Foundation, CIEN Foundation and the Carlos III Institutes of Health (to MC). TL is supported by an Alzheimer's Research UK senior fellowship. TR is supported by a grant from the Karin & Sten Mortstedt CBD Solutions AB, Stockholm, Sweden and by the National Institute for Health Research (NIHR) Queen Square Biomedical Research Unit in Dementia based at University College London Hospitals (UCLH), University College London (UCL). The views expressed are those of the authors and not necessarily those of the NIH, NHS, the NIHR or the Department of Health. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Alzheimer's disease | es_ES |
dc.subject | Amyloid | es_ES |
dc.subject | Apo J | es_ES |
dc.subject | Apolipoprotein J | es_ES |
dc.subject | Chromosome 13 dementias | es_ES |
dc.subject | Familial British dementia | es_ES |
dc.subject | Familial Danish dementia | es_ES |
dc.title | Association of clusterin with the BRI2-derived amyloid molecules ABri and ADan | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 34298087 | es_ES |
dc.format.volume | 158 | es_ES |
dc.format.page | 105452 | es_ES |
dc.identifier.doi | 10.1016/j.nbd.2021.105452 | es_ES |
dc.contributor.funder | Fundación Centro De Investigación De Enfermedades Neurológicas | es_ES |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | es_ES |
dc.contributor.funder | Ministerio de Ciencia (España) | es_ES |
dc.contributor.funder | Fundación Reina Sofía | es_ES |
dc.contributor.funder | Alzheimer's Research UK | es_ES |
dc.contributor.funder | National Institute for Health Research (Reino Unido) | es_ES |
dc.contributor.funder | University College London Hospitals NHS Foundation Trust | es_ES |
dc.contributor.funder | Imperial College London (Reino Unido) | es_ES |
dc.contributor.funder | CBD Solutions | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1095-953X | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.nbd.2021.105452 | es_ES |
dc.identifier.journal | Neurobiology of Disease | es_ES |
dc.repisalud.centro | ISCIII::Agencia de Evaluación de Tecnologías Sanitarias | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SAF2016-78603-R | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2019-110401RB- I00 | es_ES |