Amyloid- β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNF α from neuronal protection to death
Carriba, Paulina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Jimenez, S. (Universidad de Sevilla. Departamento de Bioquimica y Biologia Molecular)
Navarro, V (Universidad de Sevilla. Departamento de Bioquimica y Biologia Molecular)
Moreno-Gonzalez, I (Universidad de Malaga. Departamento de Biologia Celular, Genetica y Fisiologia)
Barneda Zahonero, Bruna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Moubarak, Rana S. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
López-Soriano, Joaquín (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gutiérrez Pérez, Antonia (Universidad de Malaga. Departamento de Biologia Celular, Genetica y Fisiologia)
Vitorica, Javier (Universidad de Sevilla. Departamento de Bioquimica y Biologia Molecular)
Comella i Carnicé, Joan Xavier 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data:	2015
Resum:	The brains of patients with Alzheimer's disease (AD) present elevated levels of tumor necrosis factor- α (TNF α), a cytokine that has a dual function in neuronal cells. On one hand, TNF α can activate neuronal apoptosis, and on the other hand, it can protect these cells against amyloid- β (A β) toxicity. Given the dual behavior of this molecule, there is some controversy regarding its contribution to the pathogenesis of AD. Here we examined the relevance of the long form of Fas apoptotic inhibitory molecule (FAIM) protein, FAIM-L, in regulating the dual function of TNF α. We detected that FAIM-L was reduced in the hippocampi of patients with AD. We also observed that the entorhinal and hippocampal cortex of a mouse model of AD (PS1xAPP) showed a reduction in this protein before the onset of neurodegeneration. Notably, cultured neurons treated with the cortical soluble fractions of these animals showed a decrease in endogenous FAIM-L, an effect that is mimicked by the treatment with A β -derived diffusible ligands (ADDLs). The reduction in the expression of FAIM-L is associated with the progression of the neurodegeneration by changing the inflammatory response mediated by TNF α in neurons. In this sense, we also demonstrate that the protection afforded by TNF α against A β toxicity ceases when endogenous FAIM-L is reduced by short hairpin RNA (shRNA) or by treatment with ADDLs. All together, these results support the notion that levels of FAIM-L contribute to determine the protective or deleterious effect of TNF α in neuronal cells.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2009SGR346 Instituto de Salud Carlos III FIS PI12_01439 Ministerio de Economía y Competitividad SAF2010-19953
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Cell death and disease, Vol. 6 (02 2015) , p. e1639, ISSN 2041-4889

DOI: 10.1038/cddis.2015.6
PMID: 25675299

13 p, 2.4 MB

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