Transient increase in sAPPα secretion in response to Aβ1-42 oligomers: an attempt of neuronal self-defense?

Abstract:

:Amyloid precursor protein (APP), a key molecule of Alzheimer disease, is metabolized in 2 antagonist pathways generating the soluble APP alpha (sAPPα) having neuroprotective properties and the beta amyloid (Aβ) peptide at the origin of neurotoxic oligomers, particularly Aβ1-42. Whether extracellular Aβ1-42 oligomers modulate the formation and secretion of sAPPα is not known. We report here that the addition of Aβ1-42 oligomers to primary cortical neurons induced a transient increase in α-secretase activity and secreted sAPPα 6-9 hours later. Preventing the generation of sAPPα by using small interfering RNAs (siRNAs) for the α-secretases ADAM10 and ADAM17 or for APP led to increased Aβ1-42 oligomer-induced cell death after 24 hours. Neuronal injuries due to oxidative stress or growth factor deprivation also generated sAPPα 7 hours later. Finally, acute injection of Aβ1-42 oligomers into wild-type mouse hippocampi induced transient secretion of sAPPα 48-72 hours 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.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Rose C,Dorard E,Audrain M,Gorisse-Hussonnois L,Cartier N,Braudeau J,Allinquant B

doi

10.1016/j.neurobiolaging.2017.09.008

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

23-35

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(17)30301-9

journal_volume

61

pub_type

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