RT Journal Article
T1 Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death.
T2 Aβ reduces FAIM-L changing the neuronal response to TNFα
A1 Carriba, P.
A1 Jimenez, S.
A1 Navarro, V.
A1 Moreno-González, Inés
A1 Barneda-Zahonero, Bruna
A1 Moubarak, R.S.
A1 Lopez-Soriano, J.
A1 Gutiérrez-Pérez, Antonia
A1 Vitorica Ferrández, Javier
A1 Comella, Joan Xavier
K1 Alzheimer, Enfermedad de
K1 Citoquinas
K1 Factor necrosante de los tumores
AB The brains of patients with Alzheimer’s disease (AD) present elevated levels of tumor necrosis factor-α (TNFα), a cytokine that hasa dual function in neuronal cells. On one hand, TNFα can activate neuronal apoptosis, and on the other hand, it can protect thesecells against amyloid-β (Aβ) toxicity. Given the dual behavior of this molecule, there is some controversy regarding its contributionto 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 TNFα. 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 (PS1M146LxAPP751sl) showed a reduction inthis protein before the onset of neurodegeneration. Notably, cultured neurons treated with the cortical soluble fractions of theseanimals showed a decrease in endogenous FAIM-L, an effect that is mimicked by the treatment with Aβ-derived diffusible ligands(ADDLs). The reduction in the expression of FAIM-L is associated with the progression of the neurodegeneration by changing theinflammatory response mediated by TNFα in neurons. In this sense, we also demonstrate that the protection afforded by TNFαagainst Aβ toxicity ceases when endogenous FAIM-L is reduced by short hairpin RNA (shRNA) or by treatment with ADDLs. Alltogether, these results support the notion that levels of FAIM-L contribute to determine the protective or deleterious effect of TNFαin neuronal cells.
PB Cell Death & Disease
YR 2015
FD 2015-02-12
LK https://hdl.handle.net/10630/36993
UL https://hdl.handle.net/10630/36993
LA eng
NO Carriba, Jimenez, Navarro, Moreno-Gonzalez, Barneda-Zahonero, Moubarak, Lopez-Soriano, Gutierrez, Vitorica, & Comella. (2015). Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death. Cell Death and Disease, 6(2).
NO This work was funded by the Spanish Government’s ‘Ministerio de Sanidad y Consumo’ (CIBERNED, CB06/05/1104 to JXC; CIBERNED grants PI2010/08 and 2013/01 to JXC, JV, and AG); ‘Ministerio de Economía y Competitividad’ (SAF2010-19953 to JXC), and ‘Instituto de Salud Carlos III’ (FIS PI12/01439 to JV; FIS PI12/01431 to AG), and by the ‘Generalitat de Catalunya’(Suport als Grups de Recerca Consolidats 2009SGR346). PC was awarded a ‘Beatriu de Pinos’ postdoctoral grant from the ‘Generalitat de Catalunya’ co-financed by the FP7-People-COFUND Programme.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026