Publicação
Advances in amyotrophic lateral sclerosis research in 2022
| dc.contributor.author | Carvalho, Mamede | |
| dc.date.accessioned | 2023-01-05T14:48:42Z | |
| dc.date.available | 2023-01-05T14:48:42Z | |
| dc.date.issued | 2023 | |
| dc.description | © 2022 Elsevier Ltd. All rights reserved. | pt_PT |
| dc.description.abstract | ALS is pathologically characterised by cytoplasmic aggregation and nuclear depletion of TAR DNA-binding protein 43 (TDP-43). This disease mechanism also occurs in about 50% of people with frontotemporal dementia. The change in distribution of TDP-43 causes dysfunction of RNA transport, transcription, and splicing. Moreover, loss of nuclear TDP-43 leads to the inclusion of intronic sequences in mature RNA (ie, cryptic exons), causing premature polyadenylation, early stop codons, and transcript degradation. Brown and colleagues showed that TDP-43 dysfunction induces inclusion of a cryptic exon in UNC13A, causing UNC13A protein dysfunction. As this protein is essential for the priming of presynaptic vesicles, its dysfunction disrupts the exocytosis of neurotransmitters. This disruption has substantial implications in both CNS pathways and motor end plates. This finding indicates a new potential target for splicing modulation treatments. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Lancet Neurol. 2023 Jan;22(1):21-22 | pt_PT |
| dc.identifier.doi | 10.1016/S1474-4422(22)00490-2 | pt_PT |
| dc.identifier.eissn | 1474-4465 | |
| dc.identifier.issn | 1474-4422 | |
| dc.identifier.uri | http://hdl.handle.net/10451/55667 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Elsevier | pt_PT |
| dc.relation.publisherversion | https://www.sciencedirect.com/journal/the-lancet-neurology | pt_PT |
| dc.title | Advances in amyotrophic lateral sclerosis research in 2022 | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 22 | pt_PT |
| oaire.citation.issue | 1 | pt_PT |
| oaire.citation.startPage | 21 | pt_PT |
| oaire.citation.title | The Lancet Neurology | pt_PT |
| oaire.citation.volume | 22 | pt_PT |
| person.familyName | de Carvalho | |
| person.givenName | Mamede | |
| person.identifier.orcid | 0000-0001-7556-0158 | |
| person.identifier.scopus-author-id | 7101893769 | |
| rcaap.rights | restrictedAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isAuthorOfPublication | dd7f55d4-c2b5-4fd2-9bd1-a9542a62f58f | |
| relation.isAuthorOfPublication.latestForDiscovery | dd7f55d4-c2b5-4fd2-9bd1-a9542a62f58f |