Amyloid-beta-induced Synapse Damage Is Mediated via Cross-linkage of Cellular Prion Proteins

作者：Bate Clive^*; Williams Alun

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286(44): 37955-37963.

DOI：10.1074/jbc.M111.248724

The cellular prion protein (PrP(C)), which is highly expressed at synapses, was identified as a receptor for the amyloid-beta (A beta) oligomers that are associated with dementia in Alzheimer disease. Here, we report that A beta oligomers secreted by 7PA2 cells caused synapse damage in cultured neurons via a PrP(C)-dependent process. Exogenous PrP(C) added to Prnp knock-out((0/0)) neurons was targeted to synapses and significantly increased A beta-induced synapse damage. In contrast, the synapse damage induced by a phospholipase A(2)-activating peptide was independent of PrP(C). In Prnp wild-type((+/+)) neurons A beta oligomers activated synaptic cytoplasmic phospholipase A(2) (cPLA(2)). In these cells, the addition of A beta oligomers triggered the translocation of cPLA(2) in synapses to cholesterol dense membranes (lipid rafts) where it formed a complex also containing A beta and PrP(C). In contrast, the addition of A beta to Prnp((0/0)) neurons did not activate synaptic cPLA(2), which remained in the cytoplasm and was not associated with A beta. Filtration assays and non-dena

• 出版日期2011-11-4