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Inhibition of Aβ aggregation and neurotoxicity by the 39-kDa receptor-associated protein

Citation

Kerr, ML and Gasperini, R and Gibbs, ME and Hou, X and Shepherd, CE and Strickland, DK and Foa, L and Lawen, A and Small, DH, Inhibition of Aβ aggregation and neurotoxicity by the 39-kDa receptor-associated protein, Journal of Neurochemistry, 112, (5) pp. 1199-1209. ISSN 0022-3042 (2010) [Refereed Article]


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

DOI: doi:10.1111/j.1471-4159.2009.06540.x

Abstract

Aggregation of b-amyloid protein (Ab) to form oligomers is considered to be a key step in generating neurotoxicity in the Alzheimer’s disease brain. Agents that bind to Ab and inhibit oligomerization have been proposed as Alzheimer’s disease therapeutics. In this study, we investigated the binding of fluorescein-labeled Ab1–42 (FluoAb1–42) to SH-SY5Y neuroblastoma cells and examined the effect of the 39-kDa receptor- associated protein (RAP), on the Ab cell interaction. FluoAb1–42 bound to the cells in a punctate pattern. Surprisingly, when RAP was added to the incubations, FluoAb1–42 and RAP were found to be co-localized on the cell surface, suggesting that RAP and Ab may bind to each other. Experiments using the purified proteins confirmed that a RAP–Ab complex was stable and resistant to sodium dodecyl sulfate. RAP also inhibited Ab oligomerization. We next examined whether RAP could inhibit the neurotoxic effects of Ab. Addition of Ab1–42 to SH-SY5Y cells caused an increase in intracellular Ca2+ that was inhibited by treatment of the Ab peptide with RAP. RAP also blocked an Ab-induced inhibition of longterm memory consolidation in 1-day-old chicks. This study demonstrates that RAP binds to Ab and is an inhibitor of the neurotoxic effects of Ab.

Item Details

Item Type:Refereed Article
Keywords:b-amyloid, aggregation, Alzheimer’s disease, calcium, memory, receptor-associated protein
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:Gasperini, R (Dr Rob Gasperini)
Author:Foa, L (Professor Lisa Foa)
Author:Small, DH (Professor David Small)
ID Code:64811
Year Published:2010
Web of Science® Times Cited:4
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-09-02
Last Modified:2012-03-01
Downloads:0

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