Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Amyloid β serves as an NGF-like neurotrophic factor or acts as a NGF antagonist depending on its concentration

Arevalo, Maria-Ángeles, Roldan, Pedro M., Chacon Fernandez, Pedro and Rodríguez-Tebar, Alfredo 2009. Amyloid β serves as an NGF-like neurotrophic factor or acts as a NGF antagonist depending on its concentration. Journal of Neurochemistry 111 (6) , pp. 1425-1433. 10.1111/j.1471-4159.2009.06412.x

Full text not available from this repository.

Abstract

In the nervous system, both the shape and connectivity of neurons are strongly influenced by soluble, extracellular factors. Indeed, we recently demonstrated that after binding to p75NTR, the common neurotrophin receptor, nerve growth factor (NGF) controls the morphology and connectivity of cultured mouse hippocampal neurons by encouraging the production of fewer yet longer dendrites, and by augmenting GABAergic connectivity. These effects of NGF are mediated by the differential expression of Enhancer-of-split 1/5 homologs and neurogenin 3. Amyloid β (Aβ), a pathogenic agent in Alzheimer’s disease (AD) is known to bind to p75NTR, hence we studied its influence on cultured hippocampal neurons. At 800 nM, Aβ(1–40) prevents NGF-induced activation of NF-κB and consequently, it depresses the expression of Enhancer-of-split 1. Thus, at this concentration, the effect of Aβ on neurons is antagonistic to those provoked by NGF and accordingly, neurons sprout more yet shorter dendrites and their GABAergic input decreases. In contrast, at lower concentration, 20 nM, the amyloid induces cellular effects similar to those induced by NGF, both in terms of gene expression, neuronal morphology, and GABAergic connectivity. Our results demonstrate that Aβ may act as a neurotrophic factor that mimics the activity of NGF. However, at higher concentrations, the amyloid behaves as an antagonist of NGF, contributing to the advent of AD.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Wiley
ISSN: 0022-3042
Last Modified: 28 Jun 2019 02:02
URI: http://orca.cf.ac.uk/id/eprint/65867

Citation Data

Cited 22 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item