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The cholesterol ester cycle regulates signalling complexes and synapse damage caused by amyloid-ß

West, E; Osborne, C; Bate, C


E West

C Osborne

C Bate


Cholesterol is required for the formation and function of some signalling platforms. In synaptosomes, amyloid-β (Aβ) oligomers, the causative agent in Alzheimer's disease, bind to cellular prion proteins (PrPC) resulting in increased cholesterol concentrations, translocation of cytoplasmic phospholipase A2 (cPLA2, also known as PLA2G4A) to lipid rafts, and activation of cPLA2. The formation of Aβ-PrPC complexes is controlled by the cholesterol ester cycle. In this study, Aβ activated cholesterol ester hydrolases, which released cholesterol from stores of cholesterol esters and stabilised Aβ-PrPC complexes, resulting in activated cPLA2. Conversely, cholesterol esterification reduced cholesterol concentrations causing the dispersal of Aβ-PrPC complexes. In cultured neurons, the cholesterol ester cycle regulated Aβ-induced synapse damage; cholesterol ester hydrolase inhibitors protected neurons, while inhibition of cholesterol esterification significantly increased Aβ-induced synapse damage. An understanding of the molecular mechanisms involved in the dispersal of signalling complexes is important as failure to deactivate signalling pathways can lead to pathology. This study demonstrates that esterification of cholesterol is a key factor in the dispersal of Aβ-induced signalling platforms involved in the activation of cPLA2 and synapse degeneration.


West, E., Osborne, C., & Bate, C. (2017). The cholesterol ester cycle regulates signalling complexes and synapse damage caused by amyloid-ß. Journal of Cell Science, 130, 3050-3059.

Journal Article Type Article
Acceptance Date Jul 26, 2017
Publication Date Sep 15, 2017
Deposit Date Dec 8, 2017
Publicly Available Date Sep 15, 2018
Journal Journal of Cell Science
Print ISSN 0021-9533
Publisher The Company of Biologists
Peer Reviewed Peer Reviewed
Volume 130
Pages 3050-3059
Public URL


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