Header

UZH-Logo

Maintenance Infos

Different effects of soluble and aggregated amyloid β42 on gene/protein expression and enzyme activity involved in insulin and APP pathways


Bartl, Jasmin; Meyer, Andrea; Brendler, Svenja; Riederer, Peter; Grünblatt, Edna (2013). Different effects of soluble and aggregated amyloid β42 on gene/protein expression and enzyme activity involved in insulin and APP pathways. Journal of Neural Transmission, 120(1):113-120.

Abstract

Although Alzheimer's dementia (AD) is not characterised any longer simply as the accumulation and deposition of amyloid beta (Aβ) peptides and hyperphosphorylation of tau proteins within the brain, excessive Aβ(42) deposition is still considered to play a major role in this illness. Aβ are able to adopt many differently aggregate forms, including amyloid fibrils as well as nonfibrillar structures (soluble Aβ(42) oligomers). It is not well-established that which Aβ(42) state is most responsible for AD or why. We wanted to verify which effects Aβ(42) oligomers and aggregated peptides have on gene expression, protein level and enzyme activity of insulin and amyloid precursor protein (APP) pathways in vitro. Human neuroblastoma cells (SH-SY5Y) were treated with varying concentrations of soluble and aggregated Aβ(42). Treatment effects on β-secretase (BACE), glycogen synthase kinase 3α (GSK3α), glycogen synthase kinase 3β (GSK3β), phosphatidylinositol-3 kinase (PI-3K), insulin-degrading enzyme (IDE), insulin-receptor substrate 1 (IRS1), insulin receptor (INSR) and monoamine oxidase B (MAO-B) were investigated via quantitative-PCR, western blot, ELISA and enzyme activity assay. We could find different effects of soluble and aggregated peptides especially on gene/protein expression of GSK3β and INSR and on GSK3β and MAO-B activity. Soluble peptides showed significant effects leading to increased gene expression and protein amount of GSK3β and to decreased level of gene and protein expression of INSR. MAO-B activity was enhanced after treatment with aggregated peptides and strongly inhibited after soluble Aβ(42) treatment. Our data might provide insights into selective effects of specific forms of Aβ(42) aggregates in AD.

Abstract

Although Alzheimer's dementia (AD) is not characterised any longer simply as the accumulation and deposition of amyloid beta (Aβ) peptides and hyperphosphorylation of tau proteins within the brain, excessive Aβ(42) deposition is still considered to play a major role in this illness. Aβ are able to adopt many differently aggregate forms, including amyloid fibrils as well as nonfibrillar structures (soluble Aβ(42) oligomers). It is not well-established that which Aβ(42) state is most responsible for AD or why. We wanted to verify which effects Aβ(42) oligomers and aggregated peptides have on gene expression, protein level and enzyme activity of insulin and amyloid precursor protein (APP) pathways in vitro. Human neuroblastoma cells (SH-SY5Y) were treated with varying concentrations of soluble and aggregated Aβ(42). Treatment effects on β-secretase (BACE), glycogen synthase kinase 3α (GSK3α), glycogen synthase kinase 3β (GSK3β), phosphatidylinositol-3 kinase (PI-3K), insulin-degrading enzyme (IDE), insulin-receptor substrate 1 (IRS1), insulin receptor (INSR) and monoamine oxidase B (MAO-B) were investigated via quantitative-PCR, western blot, ELISA and enzyme activity assay. We could find different effects of soluble and aggregated peptides especially on gene/protein expression of GSK3β and INSR and on GSK3β and MAO-B activity. Soluble peptides showed significant effects leading to increased gene expression and protein amount of GSK3β and to decreased level of gene and protein expression of INSR. MAO-B activity was enhanced after treatment with aggregated peptides and strongly inhibited after soluble Aβ(42) treatment. Our data might provide insights into selective effects of specific forms of Aβ(42) aggregates in AD.

Statistics

Citations

6 citations in Web of Science®
7 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

161 downloads since deposited on 28 Feb 2013
24 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:28 Feb 2013 14:09
Last Modified:07 Dec 2017 20:05
Publisher:Springer
ISSN:0300-9564
Additional Information:The original publication is available at www.springerlink.com
Publisher DOI:https://doi.org/10.1007/s00702-012-0852-5
PubMed ID:22782687

Download

Download PDF  'Different effects of soluble and aggregated amyloid β42 on gene/protein expression and enzyme activity involved in insulin and APP pathways'.
Preview
Content: Accepted Version
Language: English
Filetype: PDF
Size: 1MB
View at publisher