Reference : Critical role of cPLA2 in Aβ oligomer-induced neurodegeneration and memory deficit.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Social & behavioral sciences, psychology : Neurosciences & behavior
Critical role of cPLA2 in Aβ oligomer-induced neurodegeneration and memory deficit.
Desbène, Cédric []
Malaplate-Armand, Catherine []
Youssef, Ihsen []
Garcia, Pierre mailto [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 []
Neurobiology of Aging
Yes (verified by ORBilu)
New York
[en] Alzheimer's disease ; Cytosolic phospholipase A2 ; Soluble beta-amyloid oligomers
[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.
Alzheimer's disease; Cytosolic phospholipase A2; Soluble beta-amyloid oligomers; Memory; Apoptosis; Synaptotoxicity; Amyloid precursor protein
Institut National Polytechnique de Lorraine / INSERM
Researchers ; Professionals ; Students ; General public ; Others

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2012 DESBENES-MALAPLATE-YOUSSEF-GARCIA Critical role of cPLA2 in Aβ oligomer-induced neurodegeneration and memory deficit..pdfPublisher postprint863.36 kBView/Open

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