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Substrate-bound beta-amyloid peptides inhibit cell adhesion and neurite outgrowth in primary neuronal cultures
journal contribution
posted on 2023-05-17, 10:00 authored by Postuma, RB, He, WL, Nunan, J, Beyreuther, K, Masters, CL, Barrow, CJ, David SmallDavid SmallAccumulation of theβ-amyloid protein (Aβ) in the brain is an important step in the pathogenesis of Alzheimer's disease. However, the mechanism of Aβ toxicity remains unclear. Aβ can bind to the extracellular matrix, a structure that regulates adhesive events such as neurite outgrowth and synaptogenesis. The binding of Aβ to the extracellular matrix suggests that Aβ may disrupt cell-substrate interactions. Therefore, the effect of substrate-bound Aβ on the growth of isolated chick sympathetic and mouse cortical neurons was examined. Aβ1-40 and Aβ1-42 had dose-dependent effects on cell morphology. When tissue culture plates were coated with 0.1-10 ng/well Aβ, neurite outgrowth increased. Higher amounts of Aβ peptides (≥μg/well) inhibited outgrowth. The inhibitory effect was related to aggregation of the peptide, as preincubation of Aβ1-40 for 24 h at 37 °C (a process known to increase amyloid fibril formation) was necessary for inhibition of neurite outgrowth. Aβ29-42, but not Aβ1-28, also inhibited neurite outgrowth at high concentrations, demonstrating that the inhibitory domain is located within the hydrophobic C-terminal region. Aβ1-40, Aβ1-42, and Aβ29-42 also inhibited cell-substrate adhesion, indicating that the effect on neurite outgrowth may have been due to inhibition of cell adhesion. The results suggest that accumulation of Aβ may disrupt cell-adhesion mechanisms in vivo.
History
Publication title
Journal of NeurochemistryVolume
74Pagination
1122-1130ISSN
0022-3042Department/School
Menzies Institute for Medical ResearchPublisher
Wiley-Blackwell Publishing Ltd.Place of publication
United KingdomRights statement
The definitive published version is available online at: http://www3.interscience.wiley.com/Repository Status
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