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Morphological and Molecular Profiling of Amyloid-β Species in Alzheimer’s Pathogenesis

2024-10-24Journal article Open access
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dc.contributor.authorAlmeida, Zaida L.
dc.contributor.authorVaz, Daniela C.
dc.contributor.authorBrito, Rui M. M.
dc.date.accessioned2024-10-30T15:17:25Z
dc.date.available2024-10-30T15:17:25Z
dc.date.issued2024-10-24
dc.descriptionAcknowledgements Authors acknowledge funding by COMPETE and CENTRO-2020 and by Fundação para a Ciência e a Tecnologia (FCT).pt_PT
dc.descriptionFunding Open access funding provided by FCT|FCCN (b-on). Authors received funding from COMPETE and CENTRO-2020 and from Fundação para a Ciência e a Tecnologia (FCT): UIDB/00313/2020 and UIDP/00313/2020 (to Coimbra Chemistry Centre, University of Coimbra) and the doctoral fellowship SFRH/BD/137991/2018 (to Z.L.A.).pt_PT
dc.description.abstractAlzheimer’s disease (AD) is the most common form of dementia around the world (~ 65%). Here, we portray the neuropathology of AD, biomarkers, and classifcation of amyloid plaques (difuse, non-cored, dense core, compact). Tau pathology and its involvement with Aβ plaques and cell death are discussed. Amyloid cascade hypotheses, aggregation mechanisms, and molecular species formed in vitro and in vivo (on- and of-pathways) are described. Aβ42/Aβ40 monomers, dimers, trimers, Aβ‐derived difusible ligands, globulomers, dodecamers, amylospheroids, amorphous aggregates, protofbrils, fbrils, and plaques are characterized (structure, size, morphology, solubility, toxicity, mechanistic steps). An update on AD-approved drugs by regulatory agencies, along with new Aβ-based therapies, is presented. Beyond prescribing Aβ plaque disruptors, cholinergic agonists, or NMDA receptor antagonists, other therapeutic strategies (RNAi, glutaminyl cyclase inhibitors, monoclonal antibodies, secretase modulators, Aβ aggregation inhibitors, and anti-amyloid vaccines) are already under clinical trials. New drug discovery approaches based on “designed multiple ligands”, “hybrid molecules”, or “multitarget-directed ligands” are also being put forward and may contribute to tackling this highly debilitating and fatal form of human dementia.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAlmeida, Z.L., Vaz, D.C. & Brito, R.M.M. Morphological and Molecular Profiling of Amyloid-β Species in Alzheimer’s Pathogenesis. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04543-4pt_PT
dc.identifier.doihttps://doi.org/10.1007/s12035-024-04543-4pt_PT
dc.identifier.eissn1559-1182
dc.identifier.urihttp://hdl.handle.net/10400.8/10208
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationCoimbra Chemistry Center
dc.relationÀ descoberta dos determinantes estruturais na inibição de interacções proteína-proteína em doenças amilóides neurodegenerativas
dc.relation.publisherversionhttps://link.springer.com/article/10.1007/s12035-024-04543-4pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAlzheimer’s disease (AD)pt_PT
dc.subjectAmyloid-beta (Aβ) peptidept_PT
dc.subjectTau proteinpt_PT
dc.subjectProtein aggregationpt_PT
dc.subjectAmyloid plaquespt_PT
dc.subjectAβ-based therapiespt_PT
dc.titleMorphological and Molecular Profiling of Amyloid-β Species in Alzheimer’s Pathogenesispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCoimbra Chemistry Center
oaire.awardTitleÀ descoberta dos determinantes estruturais na inibição de interacções proteína-proteína em doenças amilóides neurodegenerativas
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00313%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Programático/UIDP%2F00313%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F137991%2F2018/PT
oaire.citation.endPage29pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleMolecular Neurobiologypt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamConcurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Programático
person.familyNameBarroso de Moura Cipreste Vaz
person.givenNameDaniela
person.identifier.ciencia-id801A-7761-328C
person.identifier.orcid0000-0001-7562-4676
person.identifier.ridR-5243-2017
person.identifier.scopus-author-id6602838931
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscovery518f12af-3297-4334-b00b-c06e17b2cf27
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