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Substrate-bound beta-amyloid peptides inhibit cell adhesion and neurite outgrowth in primary neuronal cultures

Citation

Postuma, RB and He, WL and Nunan, J and Beyreuther, K and Masters, CL and Barrow, CJ and Small, DH, Substrate-bound beta-amyloid peptides inhibit cell adhesion and neurite outgrowth in primary neuronal cultures, Journal of Neurochemistry, 74, (3) pp. 1122-1130. ISSN 0022-3042 (2000) [Refereed Article]


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The definitive published version is available online at: http://www3.interscience.wiley.com/

DOI: doi:10.1046/j.1471-4159.2000.741122.x

Abstract

Accumulation 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.

Item Details

Item Type:Refereed Article
Keywords: β-Amyloid; Alzheimer's disease; Neurite outgrowth; Toxicity; Cell adhesion
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Small, DH (Professor David Small)
ID Code:75365
Year Published:2000
Web of Science® Times Cited:41
Deposited By:Research Division
Deposited On:2012-01-25
Last Modified:2012-02-02
Downloads:0

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