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Machado-Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy

2019-01Journal article Restricted access
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dc.contributor.authorMatos, Carlos A.
dc.contributor.authorPereira De Almeida, Luis
dc.contributor.authorNóbrega, Clévio
dc.date.accessioned2019-04-04T10:39:07Z
dc.date.available2019-04-04T10:39:07Z
dc.date.issued2019-01
dc.description.abstractMachado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an incurable disorder, widely regarded as the most common form of spinocerebellar ataxia in the world. MJD/SCA3 arises from mutation of the ATXN3 gene, but this simple monogenic cause contrasts with the complexity of the pathogenic mechanisms that are currently admitted to underlie neuronal dysfunction and death. The aberrantly expanded protein product - ataxin-3 - is known to aggregate and generate toxic species that disrupt several cell systems, including autophagy, proteostasis, transcription, mitochondrial function and signalling. Over the years, research into putative therapeutic approaches has often been devoted to the development of strategies that counteract disease at different stages of cellular pathogenesis. Silencing the pathogenic protein, blocking aggregation, inhibiting toxic proteolytic processing and counteracting dysfunctions of the cellular systems affected have yielded promising ameliorating results in studies with cellular and animal models. The current review analyses the available studies dedicated to the investigation of MJD/SCA3 pathogenesis and the exploration of possible therapeutic strategies, focusing primarily on gene therapy and pharmacological approaches rooted on the molecular and cellular mechanisms of disease.pt_PT
dc.description.sponsorshipEuropean Union through the European social fund FEDER through the Competitive Factors Operational Program - COMPETE POPH QREN French Muscular Dystrophy Association (AFM-Telethon) Ataxia UK FEDER through the Competitive Factors Operational Program-COMPETE CENTRO-07-ST24-FEDER-002002 National Funds (PIDDAC) Portuguese Foundation for Science and Technology (FCT) UID/NEU/04539/2013 French Muscular Dystrophy Association (AFM) National Ataxia Foundation (NAF) Richard Chin and Lily Lock MachadoJoseph disease Research Fund BrainHealth 2020 - Deteccao Precoce, Neuromodulacao e Terapias Avancadas para Neuropatologias CENTRO-01-0145-FEDER-000008 Joint call for European Research Project on Rare Diseases E-Rare4/0003/2012pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1111/jnc.14541pt_PT
dc.identifier.issn0022-3042
dc.identifier.urihttp://hdl.handle.net/10400.1/12444
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.subjectAtaxin-3pt_PT
dc.subjectMachado-Joseph diseasept_PT
dc.subjectNeurodegenerationpt_PT
dc.subjectTherapeutic strategiespt_PT
dc.titleMachado-Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FNEU%2F04539%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDTI/E-Rare4%2F0003%2F2012/PT
oaire.citation.endPage28pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage8pt_PT
oaire.citation.titleJournal of Neurochemistrypt_PT
oaire.citation.volume148pt_PT
oaire.fundingStream5876
oaire.fundingStream3599-PPCDTI
person.familyNamePereira de Almeida
person.familyNameNóbrega
person.givenNameLuis
person.givenNameClévio
person.identifier30884
person.identifier.ciencia-id5911-1D34-FB6B
person.identifier.ciencia-idC510-7F41-BAF8
person.identifier.orcid0000-0001-5831-3307
person.identifier.orcid0000-0002-8312-5292
person.identifier.ridA-4605-2009
person.identifier.ridM-6047-2013
person.identifier.scopus-author-id7005988619
person.identifier.scopus-author-id24473454000
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
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscovery725ea6f8-1363-4cee-9cf2-5ac7303b3ba9
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