Fine-tuning ER stress signal transducers to treat amyotrophic lateral sclerosis
Author
dc.contributor.author
Medinas Bilches, Danilo
Author
dc.contributor.author
González, José V.
Author
dc.contributor.author
Falcon, Paulina
Author
dc.contributor.author
Hetz Flores, Claudio
Admission date
dc.date.accessioned
2018-05-25T15:18:15Z
Available date
dc.date.available
2018-05-25T15:18:15Z
Publication date
dc.date.issued
2017
Cita de ítem
dc.identifier.citation
Front. Mol. Neurosci. 10: 216
es_ES
Identifier
dc.identifier.other
10.3389/fnmol.2017.00216
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/148148
Abstract
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motoneurons and paralysis. The mechanisms underlying neuronal degeneration in ALS are starting to be elucidated, highlighting disturbances in motoneuron proteostasis. Endoplasmic reticulum (ER) stress has emerged as an early pathogenic event underlying motoneuron vulnerability and denervation in ALS. Maintenance of ER proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). Inositol-requiring enzyme 1 (IRE1) is an ER-located kinase and endoribonuclease that operates as a major ER stress transducer, mediating the establishment of adaptive and pro-apoptotic programs. Here we discuss current evidence supporting the role of ER stress in motoneuron demise in ALS and build the rational to target IRE1 to ameliorate neurodegeneration.
es_ES
Patrocinador
dc.description.sponsorship
Congressionally Directed Medical Research Programs / Muscular Dystrophy Association, 382453 /
FONDAP program, 15150012 / Millennium Institute, P09-015-F /
Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT), 11150579 /
Michael J. Fox Foundation for Parkinson's Research-Target Validation grant, 9277 /
FONDEF, ID16I10223, D11E1007 / FONDECYT, 1140549 /
US Office of Naval Research-Global (ONR-G), N62909-16-1-2003 /
US Air Force Office of Scientific Research, FA9550-16-1-0384 /
European Commission RD, MSCA-RISE, 734749 / CONICYT-Brazil, 441921/2016-7 /
ALSRP Therapeutic Idea Award, AL150111