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oai:riuma.uma.es:10630/369932026-02-03T11:29:25Zcom_10630_2254col_10630_37953
RIUMA. Repositorio Institucional de la Universidad de Málaga author Carriba, P. author Jimenez, S. author Navarro, V. author Moreno-González, Inés author Barneda-Zahonero, Bruna author Moubarak, R.S. author Lopez-Soriano, J. author Gutiérrez-Pérez, Antonia author Vitorica Ferrández, Javier author Comella, Joan Xavier 2025-01-26T19:39:20Z 2025-01-26T19:39:20Z 2015-02-12 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). https://hdl.handle.net/10630/36993 10.1038/CDDIS.2015.6 The brains of patients with Alzheimer’s disease (AD) present elevated levels of tumor necrosis factor-α (TNFα), a cytokine that has a dual function in neuronal cells. On one hand, TNFα can activate neuronal apoptosis, and on the other hand, it can protect these cells against amyloid-β (Aβ) 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 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 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 Aβ-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 TNFα in neurons. In this sense, we also demonstrate that the protection afforded by TNFα against Aβ 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 TNFα in neuronal cells. eng Atribución 4.0 Internacional Alzheimer, Enfermedad de Citoquinas Factor necrosante de los tumores Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death. journal article 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 URL https://riuma.uma.es/bitstreams/34856a17-b4bc-4adc-9cc0-f35cdf953d4c/download File MD5 85dc36c2dac90795aae8c2b941a10403 2549709 application/pdf Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death 2015.pdf