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- Title
Inhibition of Aβ aggregation and neurotoxicity by the 39-kDa receptor-associated protein.
- Authors
Kerr, Megan L.; Gasperini, Robert; Gibbs, Marie E.; Xu Hou; Shepherd, Claire E.; Strickland, Dudley K.; Foa, Lisa; Lawen, Alfons; Small, David H.
- Abstract
J. Neurochem. (2010) 112, 1199–1209. Aggregation of β-amyloid protein (Aβ) to form oligomers is considered to be a key step in generating neurotoxicity in the Alzheimer’s disease brain. Agents that bind to Aβ and inhibit oligomerization have been proposed as Alzheimer’s disease therapeutics. In this study, we investigated the binding of fluorescein-labeled Aβ1–42 (FluoAβ1–42) to SH-SY5Y neuroblastoma cells and examined the effect of the 39-kDa receptor-associated protein (RAP), on the Aβ cell interaction. FluoAβ1–42 bound to the cells in a punctate pattern. Surprisingly, when RAP was added to the incubations, FluoAβ1–42 and RAP were found to be co-localized on the cell surface, suggesting that RAP and Aβ may bind to each other. Experiments using the purified proteins confirmed that a RAP–Aβ complex was stable and resistant to sodium dodecyl sulfate. RAP also inhibited Aβ oligomerization. We next examined whether RAP could inhibit the neurotoxic effects of Aβ. Addition of Aβ1–42 to SH-SY5Y cells caused an increase in intracellular Ca2+ that was inhibited by treatment of the Aβ peptide with RAP. RAP also blocked an Aβ-induced inhibition of long-term memory consolidation in 1-day-old chicks. This study demonstrates that RAP binds to Aβ and is an inhibitor of the neurotoxic effects of Aβ.
- Subjects
AMYLOID beta-protein; OLIGOMERS; NEUROTOXICOLOGY; ALZHEIMER'S disease; NEUROBLASTOMA
- Publication
Journal of Neurochemistry, 2010, Vol 112, Issue 5, p1199
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2009.06540.x