Publication
Mutant Ataxin-2 expression in aged animals aggravates neuropathological features associated with Spinocerebellar Ataxia type 2
| dc.contributor.author | Afonso, Inês T. | |
| dc.contributor.author | Lima, Patrícia | |
| dc.contributor.author | Conceição, André | |
| dc.contributor.author | Matos, Carlos A | |
| dc.contributor.author | Nóbrega, Clévio | |
| dc.date.accessioned | 2022-10-14T09:51:06Z | |
| dc.date.available | 2022-10-14T09:51:06Z | |
| dc.date.issued | 2022-10-07 | |
| dc.date.updated | 2022-10-13T12:59:35Z | |
| dc.description.abstract | Spinocerebellar ataxia type 2 (SCA2) is a rare autosomal, dominantly inherited disease, in which the affected individuals have a disease onset around their third life decade. The molecular mechanisms underlying SCA2 are not yet completely understood, for which we hypothesize that aging plays a role in SCA2 molecular pathogenesis. In this study, we performed a striatal injection of mutant ataxin-2 mediated by lentiviral vectors, in young and aged animals. Twelve weeks post-injection, we analyzed the striatum for SCA2 neuropathological features and specific aging hallmarks. Our results show that aged animals had a higher number of mutant ataxin-2 aggregates and more neuronal marker loss, compared to young animals. Apoptosis markers, cleaved caspase-3, and cresyl violet staining also indicated increased neuronal death in the aged animal group. Additionally, mRNA levels of microtubule-associated protein 1 light-chain 3B (LC3) and sequestosome-1 (SQSTM1/p62) were altered in the aged animal group, suggesting autophagic pathway dysfunction. This work provides evidence that aged animals injected with expanded ataxin-2 had aggravated SCA2 disease phenotype, suggesting that aging plays an important role in SCA2 disease onset and disease progression. | pt_PT |
| dc.description.sponsorship | ALG-01-0145-FEDER-2948; PPBI-POCI-01-0145-FEDER-022122 | |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | International Journal of Molecular Sciences 23 (19): 11896 (2022) | pt_PT |
| dc.identifier.doi | 10.3390/ijms231911896 | pt_PT |
| dc.identifier.eissn | 1422-0067 | |
| dc.identifier.uri | http://hdl.handle.net/10400.1/18390 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | MDPI | pt_PT |
| dc.relation | Connecting mutant Ataxin-2 and synaptic disfunction: are stress granules the link | |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
| dc.subject | Spinocerebellar ataxia type 2 | pt_PT |
| dc.subject | Aging | pt_PT |
| dc.subject | Polyglutamine diseases | pt_PT |
| dc.subject | Autophagy | pt_PT |
| dc.subject | Neurodegeneration | pt_PT |
| dc.title | Mutant Ataxin-2 expression in aged animals aggravates neuropathological features associated with Spinocerebellar Ataxia type 2 | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | Connecting mutant Ataxin-2 and synaptic disfunction: are stress granules the link | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT//2020.07892.BD/PT | |
| oaire.citation.issue | 19 | |
| oaire.citation.startPage | 11896 | |
| oaire.citation.title | International Journal of Molecular Sciences | pt_PT |
| oaire.citation.volume | 23 | |
| person.familyName | Vieira da Conceição | |
| person.familyName | Albuquerque Andrade de Matos | |
| person.familyName | Nóbrega | |
| person.givenName | André Filipe | |
| person.givenName | Carlos Adriano | |
| person.givenName | Clévio | |
| person.identifier.ciencia-id | F710-8071-CA06 | |
| person.identifier.ciencia-id | DC14-C299-222A | |
| person.identifier.ciencia-id | C510-7F41-BAF8 | |
| person.identifier.orcid | 0000-0002-9348-3560 | |
| person.identifier.orcid | 0000-0002-9019-7569 | |
| person.identifier.orcid | 0000-0002-8312-5292 | |
| person.identifier.rid | M-6047-2013 | |
| person.identifier.scopus-author-id | 24473454000 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
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