Skip to Content
MilliporeSigma
  • α-Synuclein increases β-amyloid secretion by promoting β-/γ-secretase processing of APP.

α-Synuclein increases β-amyloid secretion by promoting β-/γ-secretase processing of APP.

PloS one (2017-02-12)
Hazel L Roberts, Bernard L Schneider, David R Brown
ABSTRACT

α-Synuclein misfolding and aggregation is often accompanied by β-amyloid deposition in some neurodegenerative diseases. We hypothesised that α-synuclein promotes β-amyloid production from APP. β-Amyloid levels and APP amyloidogenic processing were investigated in neuronal cell lines stably overexpressing wildtype and mutant α-synuclein. γ-Secretase activity and β-secretase expression were also measured. We show that α-synuclein expression induces β-amyloid secretion and amyloidogenic processing of APP in neuronal cell lines. Certain mutations of α-synuclein potentiate APP amyloidogenic processing. γ-Secretase activity was not enhanced by wildtype α-synuclein expression, however β-secretase protein levels were induced. Furthermore, a correlation between α-synuclein and β-secretase protein was seen in rat brain striata. Iron chelation abolishes the effect of α-synuclein on neuronal cell β-amyloid secretion, whereas overexpression of the ferrireductase enzyme Steap3 is robustly pro-amyloidogenic. We propose that α-synuclein promotes β-amyloid formation by modulating β-cleavage of APP, and that this is potentially mediated by the levels of reduced iron and oxidative stress.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Aggregated a-Synuclein Antibody, clone 5G4, clone 5G4, from mouse, purified by affinity chromatography
Sigma-Aldrich
Anti-Synuclein α Antibody, Chemicon®, from sheep