Transient increase in sAPPα secretion in response to Aß1-42 oligomers: an attempt of neuronal self-defense?

Publication date: Available online 19 September 2017
Source:Neurobiology of Aging
Author(s): Christiane Rose, Emilie Dorard, Mickael Audrain, Lucie Gorisse-Hussonnois, Nathalie Cartier, Jérome Braudeau, Bernadette Allinquant
Amyloid Precursor Protein (APP), key molecule of Alzheimer disease is metabolized in two antagonist pathways generating the sAPPα having neuroprotective properties and the amyloid peptide (Aß) at the origin of neurotoxic oligomers, particularly Aß1-42. Whether extracellular Aß1-42 oligomers modulate the formation and secretion of sAPPα is not known. We report here that the addition of Aß1-42 oligomers to primary cortical neurons induced a transient increase in alpha secretase activity and secreted sAPPα 6-9 h later. Preventing the generation of sAPPα by using siRNAs for the alpha secretases ADAM10 and ADAM17, or for APP led to increased Aß1-42 oligomer-induced cell death after 24 h. Neuronal injuries due to oxidative stress or growth factor deprivation also generated sAPPα 7h later. Finally, acute injection of Aß1-42 oligomers into wild type mouse hippocampi induced transient secretion of sAPPα 48-72 h later. Altogether, these data suggest that neurons respond to stress by generating sAPPα for their survival. These data must be taken into account when interpreting sAPPα levels as a biomarker in neurological disorders.



http://ift.tt/2hi99Tj