|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|4932514||1363431||2018||13 صفحه PDF||سفارش دهید||دانلود کنید|
Amyloid precursor protein (APP), a key molecule of Alzheimer disease, is metabolized in 2 antagonist pathways generating the soluble APP alpha (sAPPÎ±) having neuroprotective properties and the beta amyloid (AÎ²) peptide at the origin of neurotoxic oligomers, particularly AÎ²1-42. Whether extracellular AÎ²1-42 oligomers modulate the formation and secretion of sAPPÎ± is not known. We report here that the addition of AÎ²1-42 oligomers to primary cortical neurons induced a transient increase in Î±-secretase activity and secreted sAPPÎ± 6-9Â hours later. Preventing the generation of sAPPÎ± by using small interfering RNAs (siRNAs) for the Î±-secretases ADAM10 and ADAM17 or for APP led to increased AÎ²1-42 oligomer-induced cell death after 24Â hours. Neuronal injuries due to oxidative stress or growth factor deprivation also generated sAPPÎ± 7 hours later. Finally, acute injection of AÎ²1-42 oligomers into wild-type mouse hippocampi induced transient secretion of sAPPÎ± 48-72Â hours later. Altogether, these data suggest that neurons respond to stress by generating sAPPÎ± for their survival. These data must be taken into account when interpreting sAPPÎ± levels as a biomarker in neurological disorders.
Journal: Neurobiology of Aging - Volume 61, January 2018, Pages 23-35