Abstract
a-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.
Original language | English |
---|---|
Article number | e0171925 |
Journal | PLoS ONE |
Volume | 12 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Feb 2017 |
ASJC Scopus subject areas
- General Medicine
- General Biochemistry,Genetics and Molecular Biology
- General Agricultural and Biological Sciences
Fingerprint
Dive into the research topics of 'α-Synuclein increases β-amyloid secretion by promoting β-/γ-secretase processing of APP'. Together they form a unique fingerprint.Datasets
-
Dataset for research paper: α-Synuclein Increases β-Amyloid Secretion by Promoting β-/γ-Secretase Processing of APP
Roberts, H. (Creator) & Brown, D. (Creator), University of Bath, 2016
DOI: 10.15125/BATH-00310
Dataset