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Amyloid β serves as an NGF‐like neurotrophic factor or acts as a NGF antagonist depending on its concentration
Author(s) -
Arevalo MariaÁngeles,
Roldan Pedro M.,
Chacón Pedro J.,
RodríguezTebar Alfredo
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06412.x
Subject(s) - nerve growth factor , neurotrophin , gabaergic , low affinity nerve growth factor receptor , neurotrophic factors , hippocampal formation , neurotrophin 3 , antagonist , brain derived neurotrophic factor , neuroscience , microbiology and biotechnology , chemistry , extracellular , endocrinology , medicine , biology , receptor , biochemistry , inhibitory postsynaptic potential
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 p75 NTR , 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 p75 NTR , 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.