Premium
Inhibition of Aβ aggregation and neurotoxicity by the 39‐kDa receptor‐associated protein
Author(s) -
Kerr Megan L.,
Gasperini Robert,
Gibbs Marie E.,
Hou Xu,
Shepherd Claire E.,
Strickland Dudley K.,
Foa Lisa,
Lawen Alfons,
Small David H.
Publication year - 2010
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.1471-4159.2009.06540.x
Subject(s) - neurotoxicity , receptor , intracellular , chemistry , peptide , sodium dodecyl sulfate , biochemistry , microbiology and biotechnology , biology , toxicity , organic chemistry
J. Neurochem. (2010) 112 , 1199–1209. Abstract 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 Aβ 1–42 (FluoAβ 1–42 ) to SH‐SY5Y neuroblastoma cells and examined the effect of the 39‐kDa receptor‐associated protein (RAP), on the Aβ cell interaction. FluoAβ 1–42 bound to the cells in a punctate pattern. Surprisingly, when RAP was added to the incubations, FluoAβ 1–42 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 Aβ 1–42 to SH‐SY5Y cells caused an increase in intracellular Ca 2+ 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.