Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-β
Soluble amyloid-β (Aβ) oligomers, a key driver of pathogenesis in Alzheimer disease, bind to cellular prion proteins (PrP C ) expressed on synaptosomes resulting in increased cholesterol concentrations, movement of cytoplasmic phospholipase A 2 (cPLA 2 ) to lipid rafts and activation of cPLA 2 . The...
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Series: | Journal of Experimental Neuroscience |
Online Access: | https://doi.org/10.1177/1179069517733096 |
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doaj-e1e388cf73f84b57a1d9cc6dbc1485922020-11-25T02:23:02ZengSAGE PublishingJournal of Experimental Neuroscience1179-06952017-10-011110.1177/1179069517733096Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-βClive BateSoluble amyloid-β (Aβ) oligomers, a key driver of pathogenesis in Alzheimer disease, bind to cellular prion proteins (PrP C ) expressed on synaptosomes resulting in increased cholesterol concentrations, movement of cytoplasmic phospholipase A 2 (cPLA 2 ) to lipid rafts and activation of cPLA 2 . The formation of Aβ-PrP C -cPLA 2 complexes was controlled by the cholesterol ester cycle. Thus, Aβ activated cholesterol ester hydrolases which released cholesterol from stores of cholesterol esters; the increased cholesterol concentrations stabilised Aβ-PrP C -cPLA 2 complexes. Conversely, cholesterol esterification reduced cholesterol concentrations causing the dispersal of Aβ-PrP C -cPLA 2 . In cultured neurons, the cholesterol ester cycle regulated Aβ-induced synapse damage; inhibition of cholesterol ester hydrolases protected neurons, whereas inhibition of cholesterol esterification increased the Aβ-induced synapse damage. Here, I speculate that a failure to deactivate signalling pathways can lead to pathology. Consequently, the esterification of cholesterol is a key factor in the dispersal of Aβ-induced signalling platforms and synapse degeneration.https://doi.org/10.1177/1179069517733096 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Clive Bate |
spellingShingle |
Clive Bate Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-β Journal of Experimental Neuroscience |
author_facet |
Clive Bate |
author_sort |
Clive Bate |
title |
Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-β |
title_short |
Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-β |
title_full |
Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-β |
title_fullStr |
Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-β |
title_full_unstemmed |
Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-β |
title_sort |
breaking the cycle, cholesterol cycling, and synapse damage in response to amyloid-β |
publisher |
SAGE Publishing |
series |
Journal of Experimental Neuroscience |
issn |
1179-0695 |
publishDate |
2017-10-01 |
description |
Soluble amyloid-β (Aβ) oligomers, a key driver of pathogenesis in Alzheimer disease, bind to cellular prion proteins (PrP C ) expressed on synaptosomes resulting in increased cholesterol concentrations, movement of cytoplasmic phospholipase A 2 (cPLA 2 ) to lipid rafts and activation of cPLA 2 . The formation of Aβ-PrP C -cPLA 2 complexes was controlled by the cholesterol ester cycle. Thus, Aβ activated cholesterol ester hydrolases which released cholesterol from stores of cholesterol esters; the increased cholesterol concentrations stabilised Aβ-PrP C -cPLA 2 complexes. Conversely, cholesterol esterification reduced cholesterol concentrations causing the dispersal of Aβ-PrP C -cPLA 2 . In cultured neurons, the cholesterol ester cycle regulated Aβ-induced synapse damage; inhibition of cholesterol ester hydrolases protected neurons, whereas inhibition of cholesterol esterification increased the Aβ-induced synapse damage. Here, I speculate that a failure to deactivate signalling pathways can lead to pathology. Consequently, the esterification of cholesterol is a key factor in the dispersal of Aβ-induced signalling platforms and synapse degeneration. |
url |
https://doi.org/10.1177/1179069517733096 |
work_keys_str_mv |
AT clivebate breakingthecyclecholesterolcyclingandsynapsedamageinresponsetoamyloidb |
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