Article (Scientific journals)
Critical role of cPLA2 in Aβ oligomer-induced neurodegeneration and memory deficit.
Desbène, Cédric; Malaplate-Armand, Catherine; Youssef, Ihsen et al.
2012In Neurobiology of Aging, 33 (6), p. 1123-e17-1123-e29
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Keywords :
Alzheimer's disease; Cytosolic phospholipase A2; Soluble beta-amyloid oligomers
Abstract :
[en] Soluble beta-amyloid (Aβ) oligomers are considered to putatively play a critical role in the early synapse loss and cognitive impairment observed in Alzheimer's disease. We previously demonstrated that Aβ oligomers activate cytosolic phospholipase A2 (cPLA2), which specifically releases arachidonic acid from membrane phospholipids. We here observed that cPLA2 gene inactivation prevented the alterations of cognitive abilities and the reduction of hippocampal synaptic markers levels noticed upon a single intracerebroventricular injection of Aβ oligomers in wild type mice. We further demonstrated that the Aβ oligomer-induced sphingomyelinase activation was suppressed and that phosphorylation of Akt/protein kinase B (PKB) was preserved in neuronal cells isolated from cPLA2−/− mice. Interestingly, expression of the Aβ precursor protein (APP) was reduced in hippocampus homogenates and neuronal cells from cPLA2−/− mice, but the relationship with the resistance of these mice to the Aβ oligomer toxicity requires further investigation. These results therefore show that cPLA2 plays a key role in the Aβ oligomer-associated neurodegeneration, and as such represents a potential therapeutic target for the treatment of Alzheimer's disease. Keywords Alzheimer's disease; Cytosolic phospholipase A2; Soluble beta-amyloid oligomers; Memory; Apoptosis; Synaptotoxicity; Amyloid precursor protein
Research center :
Institut National Polytechnique de Lorraine / INSERM
Disciplines :
Biochemistry, biophysics & molecular biology
Neurosciences & behavior
Author, co-author :
Desbène, Cédric
Malaplate-Armand, Catherine
Youssef, Ihsen
Garcia, Pierre  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Stenger, Christophe
Sauvée, Mathilde
Fischer, Nicolas
Rimet, Dorine
Koziel, Violette
Escanyé, Marie-Christine
Oster, Thierry
Kriem, Baddredine
Yen, Frances T
Pillot, Thierry
Olivier, Jean-Luc
More authors (5 more) Less
External co-authors :
yes
Language :
English
Title :
Critical role of cPLA2 in Aβ oligomer-induced neurodegeneration and memory deficit.
Publication date :
June 2012
Journal title :
Neurobiology of Aging
ISSN :
1558-1497
Publisher :
Elsevier, New York, United States - New York
Volume :
33
Issue :
6
Pages :
1123-e17-1123-e29
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 02 July 2014

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