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dc.contributor.author
Marcora, Maria Silvina
dc.contributor.author
Belfiori Carrasco, Lautaro Francisco
dc.contributor.author
Bocai, Nadia Irina
dc.contributor.author
Morelli, Laura
dc.contributor.author
Castaño, Eduardo Miguel
dc.date.available
2018-02-27T18:13:37Z
dc.date.issued
2017-12
dc.identifier.citation
Marcora, Maria Silvina; Belfiori Carrasco, Lautaro Francisco; Bocai, Nadia Irina; Morelli, Laura; Castaño, Eduardo Miguel; Amyloid-β42 clearance and neuroprotection mediated by X-box binding protein 1 signaling decline with aging in the Drosophila brain; Elsevier Science Inc; Neurobiology of Aging; 60; 12-2017; 57-70
dc.identifier.issn
0197-4580
dc.identifier.uri
http://hdl.handle.net/11336/37290
dc.description.abstract
The unfolded protein response (UPR) may be pathogenically related to Alzheimer's disease. Yet, the effects of chronic amyloid-β42 (Aβ42) accumulation and UPR activation upon neurotoxicity remain unclear. Here, we show that neuronal Aβ42 expression in Drosophila activated the inositol-requiring protein-1/X-box binding protein 1 (XBP1) UPR branch before the onset of behavioral impairment and persisted with aging. Early upregulation of hsc3/BiP, a target of XBP1 and activating transcription factor 6 pathways, was also sustained in old animals. Downregulation of XBP1 enhanced neurotoxicity and the accumulation of Aβ42 and polyubiquitinated proteins. Consistently, overexpression of spliced XBP1 reduced Aβ42 and improved geotaxis in old flies. The activation of protein kinase RNA-like endoplasmic reticulum (ER) kinase contributed to the age-dependent geotaxis deficit. Spliced XBP1 gene targets ER degradation-enhancing mannosidase-like protein 1, ER degradation-enhancing mannosidase-like protein 2, and HRD1 were elevated in 5-day-old Aβ42-expressing flies as compared to controls but not in 18-day-old flies. Our results indicate that inositol-requiring protein-1/XBP1 activation is neuroprotective and enhances Aβ42 clearance. They also suggest that such response becomes inefficient with aging.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
ALZHEIMER'S DISEASE
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AMYLOID Β
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DROSOPHILA
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NEURODEGENERATION
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UNFOLDED PROTEIN RESPONSE
dc.subject
XBP1
dc.subject.classification
Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Amyloid-β42 clearance and neuroprotection mediated by X-box binding protein 1 signaling decline with aging in the Drosophila brain
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-01-12T19:26:45Z
dc.journal.volume
60
dc.journal.pagination
57-70
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Marcora, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Belfiori Carrasco, Lautaro Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Bocai, Nadia Irina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.journal.title
Neurobiology of Aging
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.neurobiolaging.2017.08.012
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0197458017302683
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