Pro-inflammatory conditions promote neuronal damage mediated by Amyloid Precursor Protein and decrease its phagocytosis and degradation by microglial cells in culture

von Bernhardi R.; Ramirez G.; Toro, R; Eugenín J.

Abstract

Aberrant handling of Amyloid Precursor Protein (APP) and β-amyloid (Aβ), glial activation and inflammation are key events in Alzheimer's disease. We set out to determine the role of inflammation on microglial reactivity against APP. We studied microglia-mediated neurotoxicity, uptake and degradation of a biotinylated APP construct (biotin-APP-C-244). APP, in contrast to Aβ, only induced mild activation of glial cells. However, under pro-inflammatory conditions, APP induced microglial-mediated cytotoxicity. Biotin-APP-C-244 or lipopolysaccharide and interferon-gamma (LPS + IFNγ), administered separately, did not change reduction metabolism of microglia. However, biotin-APP-C-244 + (LPS + IFNγ) increased microglial reactivity and decreased reduction metabolism by 75% (P < 0.001). Biotin-APP-C-244 was readily taken up by microglial cells; 80% was phagocytosed at 2 h. In the presence of LPS + IFNγ, phagocytosis of biotin-APP-C-244 was reduced at 2 h; and cell damage was evident after 4 h. Our results support our hypothesis that, in neuroinflammation, microglial scavenger function is impaired and reactivity against APP enhanced as an initial step for neurodegeneration. © 2006 Elsevier Inc. All rights reserved.

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Título según WOS: Pro-inflammatory conditions promote neuronal damage mediated by Amyloid Precursor Protein and decrease its phagocytosis and degradation by microglial cells in culture
Título según SCOPUS: Pro-inflammatory conditions promote neuronal damage mediated by Amyloid Precursor Protein and decrease its phagocytosis and degradation by microglial cells in culture
Título de la Revista: NEUROBIOLOGY OF DISEASE
Volumen: 26
Número: 1
Editorial: ACADEMIC PRESS INC ELSEVIER SCIENCE
Fecha de publicación: 2007
Página de inicio: 153
Página final: 164
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S0969996106003196
DOI:

10.1016/j.nbd.2006.12.006

Notas: ISI, SCOPUS