| dc.contributor.author | Woehlbier, U. [Univ Mayor, Ctr Genom & Bioinformat, Fac Sci, Camino Piramide] | es_CL |
| dc.contributor.author | Manque, P. A.[Univ Mayor, Ctr Genom & Bioinformat, Fac Sci] | es_CL |
| dc.contributor.author | Hernández, M. F. [Univ Mayor, Ctr Genom & Bioinformat, Fac Sci, Camino Piramide] | es_CL |
| dc.contributor.author | Bergmann, C. A. [Univ Mayor, Ctr Genom & Bioinformat, Fac Sci, Camino Piramide] | es_CL |
| dc.contributor.author | Cortez, C. [Univ Mayor, Ctr Genom & Bioinformat, Fac Sci] | es_CL |
| dc.contributor.author | Cortés, B. I. [Univ Mayor, Ctr Genom & Bioinformat, Fac Sci] | es_CL |
| dc.contributor.author | Labrador, L. [Univ Mayor, Ctr Genom & Bioinformat, Fac Sci] | es_CL |
| dc.contributor.author | Arcos, J. [Univ Mayor, Ctr Genom & Bioinformat, Fac Sci] | es_CL |
| dc.contributor.author | Vicencio, E. [Univ Mayor, Ctr Genom & Bioinformat, Fac Sci] | es_CL |
| dc.contributor.author | Nassif, M. [Univ Mayor, Ctr Genom & Bioinformat, Fac Sci] | es_CL |
| dc.date.accessioned | 2020-04-12T14:11:55Z | |
| dc.date.accessioned | 2020-04-14T15:46:15Z | |
| dc.date.available | 2020-04-12T14:11:55Z | |
| dc.date.available | 2020-04-14T15:46:15Z | |
| dc.date.issued | 2019 | es_CL |
| dc.identifier.citation | Beltran, S., Nassif, M., Vicencio, E., Arcos, J., Labrador, L., Cortes, B. I., ... & Matamala, J. M. (2019). Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis. Molecular neurodegeneration, 14(1), 1-18. | es_CL |
| dc.identifier.issn | 1750-1326 | es_CL |
| dc.identifier.uri | https://doi.org/10.1186/s13024-019-0313-9 | es_CL |
| dc.identifier.uri | http://repositorio.umayor.cl/xmlui/handle/sibum/6683 | |
| dc.description.abstract | BackgroundAmyotrophic lateral sclerosis (ALS) is a multifactorial fatal motoneuron disease without a cure. Ten percent of ALS cases can be pointed to a clear genetic cause, while the remaining 90% is classified as sporadic. Our study was aimed to uncover new connections within the ALS network through a bioinformatic approach, by which we identified C13orf18, recently named Pacer, as a new component of the autophagic machinery and potentially involved in ALS pathogenesis.MethodsInitially, we identified Pacer using a network-based bioinformatic analysis. Expression of Pacer was then investigated in vivo using spinal cord tissue from two ALS mouse models (SOD1(G93A) and TDP43(A315T)) and sporadic ALS patients. Mechanistic studies were performed in cell culture using the mouse motoneuron cell line NSC34. Loss of function of Pacer was achieved by knockdown using short-hairpin constructs. The effect of Pacer repression was investigated in the context of autophagy, SOD1 aggregation, and neuronal death.ResultsUsing an unbiased network-based approach, we integrated all available ALS data to identify new functional interactions involved in ALS pathogenesis. We found that Pacer associates to an ALS-specific subnetwork composed of components of the autophagy pathway, one of the main cellular processes affected in the disease. Interestingly, we found that Pacer levels are significantly reduced in spinal cord tissue from sporadic ALS patients and in tissues from two ALS mouse models. In vitro, Pacer deficiency lead to impaired autophagy and accumulation of ALS-associated protein aggregates, which correlated with theinduction of cell death.ConclusionsThis study, therefore, identifies Pacer as a new regulator of proteostasis associated with ALS pathology. | es_CL |
| dc.description.sponsorship | Anillo projectComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)CONICYT PIA/ANILLOS [ACT1109]; FONDECYT RegularComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)CONICYT FONDECYT [1150743, 1161284]; FIDUM [100739]; FONDECYT postdoctoral fellowshipComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)CONICYT FONDECYT [3140110]; FONDECYT IniciacionComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)CONICYT FONDECYT [11160288, 11150579, 11180546]; Muscular Dystrophy AssociationMuscular Dystrophy Association [575897, 382453]; ALS Association [468]; Millennium InstituteTakeda Pharmaceutical Company Ltd [P09-015-F]; FONDAP programComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)CONICYT FONDAP [15150012]; Frick Foundation [20014-15]; ALS Therapy Alliance [2014-F-059]; CONICYT-USA [2013-0003]; ALSRP Therapeutic Idea Award [AL150111]; Vlaams Instituut voor Biotechnologie (VIB); Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO)FWO [G013715N, G044518N, EOS MODEL-IDI 30826052]; Belgian science policy office (BELSPO)Belgian Federal Science Policy Office [IAP 7/32]; Flemish Government [Methusalem BOF09/01M00709, BOF16/MET_V/007] | es_CL |
| dc.description.sponsorship | This work was funded by Anillo project ACT1109 (PM and CH), FONDECYT Regular 1150743 (UW), FIDUM 100739 (UW), FONDECYT postdoctoral fellowship 3140110 (MN), FONDECYT Iniciacion 11160288 (MN), Muscular Dystrophy Association 575897 (DBM), ALS Association 468 (DBM), FONDECYT Iniciacion 11150579 (DBM), FONDECYT Iniciacion 11180546 (DRR), FONDECYT Regular 1161284 (SM). We also thank Millennium Institute No. P09-015-F FONDAP program 15150012 (CH and SM), the Frick Foundation 20014-15 (CH), ALS Therapy Alliance 2014-F-059 (CH), Muscular Dystrophy Association 382453 (CH), CONICYT-USA 2013-0003, and ALSRP Therapeutic Idea Award AL150111 (CH). We would like to thank Robert H. Brown (UMASS), Daryl Bosco (UMASS), Diane McKenna-Yasek (UMMS) and Isabel Constantino (Massachusetts General Hospital) for their procurement of human tissue samples. Research in the group of MJMB is supported by the Vlaams Instituut voor Biotechnologie (VIB), by grants from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO) (G013715N, G044518N, EOS MODEL-IDI 30826052), from the Belgian science policy office (BELSPO)(IAP 7/32) and from the Flemish Government - accorded to Prof. Vandenabeele (Methusalem BOF09/01M00709 and BOF16/MET_V/007). | es_CL |
| dc.language.iso | en | es_CL |
| dc.publisher | BMC | es_CL |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Chile | |
| dc.source | Mol. Neurodegener., MAR, 2019. 14 | |
| dc.subject | Neurosciences | es_CL |
| dc.title | Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis | es_CL |
| dc.type | Artículo | es_CL |
| umayor.facultad | CIENCIAS | |
| umayor.politicas.sherpa/romeo | DOAJ Gold, Green Published | es_CL |
| umayor.indexado | WOS:000462974500002 | es_CL |
| umayor.indexado | PMID: 30917850 | es_CL |
| dc.identifier.doi | DOI: 10.1186/s13024-019-0313-9 | es_CL] |
| umayor.indicadores.wos-(cuartil) | Q1 | es_CL |
| umayor.indicadores.scopus-(scimago-sjr) | SCIMAGO/ INDICE H: 66 H | es_CL |