Publication
Autophagy in Spinocerebellar Ataxia Type 3: From pathogenesis to therapeutics
| dc.contributor.author | Paulino, Rodrigo | |
| dc.contributor.author | Nóbrega, Clévio | |
| dc.date.accessioned | 2023-05-02T13:46:43Z | |
| dc.date.available | 2023-05-02T13:46:43Z | |
| dc.date.issued | 2023-04-17 | |
| dc.date.updated | 2023-04-27T13:51:35Z | |
| dc.description.abstract | Machado–Joseph disease (MJD) or spinocerebellar ataxia 3 (SCA3) is a rare, inherited, monogenic, neurodegenerative disease, and the most common SCA worldwide. MJD/SCA3 causative mutation is an abnormal expansion of the triplet CAG at exon 10 within the ATXN3 gene. The gene encodes for ataxin-3, which is a deubiquitinating protein that is also involved in transcriptional regulation. In normal conditions, the ataxin-3 protein polyglutamine stretch has between 13 and 49 glutamines. However, in MJD/SCA3 patients, the size of the stretch increases from 55 to 87, contributing to abnormal protein conformation, insolubility, and aggregation. The formation of aggregates, which is a hallmark of MJD/SCA3, compromises different cell pathways, leading to an impairment of cell clearance mechanisms, such as autophagy. MJD/SCA3 patients display several signals and symptoms in which the most prominent is ataxia. Neuropathologically, the regions most affected are the cerebellum and the pons. Currently, there are no disease-modifying therapies, and patients rely only on supportive and symptomatic treatments. Due to these facts, there is a huge research effort to develop therapeutic strategies for this incurable disease. This review aims to bring together current state-of-the-art strategies regarding the autophagy pathway in MJD/SCA3, focusing on evidence for its impairment in the disease context and, importantly, its targeting for the development of pharmacological and gene-based therapies. | pt_PT |
| dc.description.sponsorship | CureCSB project | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | International Journal of Molecular Sciences 24 (8): 7405 (2023) | pt_PT |
| dc.identifier.doi | 10.3390/ijms24087405 | pt_PT |
| dc.identifier.eissn | 1422-0067 | |
| dc.identifier.uri | http://hdl.handle.net/10400.1/19510 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | MDPI | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
| dc.subject | Machado–Joseph disease | pt_PT |
| dc.subject | Sspinocerebellar ataxia type 3 | pt_PT |
| dc.subject | Autophagy | pt_PT |
| dc.subject | Ataxin-3 | pt_PT |
| dc.subject | Neurodegeneration | pt_PT |
| dc.title | Autophagy in Spinocerebellar Ataxia Type 3: From pathogenesis to therapeutics | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.issue | 8 | pt_PT |
| oaire.citation.startPage | 7405 | pt_PT |
| oaire.citation.title | International Journal of Molecular Sciences | pt_PT |
| oaire.citation.volume | 24 | pt_PT |
| person.familyName | Trinca Paulino | |
| person.familyName | Nóbrega | |
| person.givenName | Rodrigo | |
| person.givenName | Clévio | |
| person.identifier.ciencia-id | D816-ED6E-1632 | |
| person.identifier.ciencia-id | C510-7F41-BAF8 | |
| person.identifier.orcid | 0000-0002-8312-5292 | |
| person.identifier.rid | M-6047-2013 | |
| person.identifier.scopus-author-id | 24473454000 | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isAuthorOfPublication | 681336e3-fe32-4f86-aabc-6fed990dff17 | |
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| relation.isAuthorOfPublication.latestForDiscovery | 725ea6f8-1363-4cee-9cf2-5ac7303b3ba9 |