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


Reference:

Roberts, H. L., Schneider, B. L. and Brown, D., 2017. α-Synuclein increases β-amyloid secretion by promoting β-/γ-secretase processing of APP. PLoS ONE, 12 (2), e0171925.

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http://dx.doi.org/10.1371/journal.pone.0171925

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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.

Details

Item Type Articles
CreatorsRoberts, H. L., Schneider, B. L. and Brown, D.
DOI10.1371/journal.pone.0171925
Related URLs
URLURL Type
http://www.scopus.com/inward/record.url?scp=85012141228&partnerID=8YFLogxKUNSPECIFIED
Uncontrolled Keywordsmedicine(all),biochemistry, genetics and molecular biology(all),agricultural and biological sciences(all)
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code56066

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