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J Neurochem. 2015 Aug;134(4):611-7. doi: 10.1111/jnc.13166. Epub 2015 Jun 10.

Dextran sulfate sodium inhibits amyloid-β oligomer binding to cellular prion protein.

Author information

1
Faculty of Pharmacy, Keio University, Tokyo, Japan.

Abstract

Amyloid-β peptide (Aβ), especially its oligomeric form, is believed to play an important role in the pathogenesis of Alzheimer's disease (AD). To this end, the binding of Aβ oligomer to cellular prion protein (PrP(C)) plays an important role in synaptic dysfunction in a mouse model of AD. Here, we have screened for compounds that inhibit Aβ oligomer binding to PrP(C) from medicines already used clinically (Mizushima Approved Medicine Library 1), and identified dextran sulfate sodium (DSS) as a candidate. In a cell-free assay, DSS inhibited Aβ oligomer binding to PrP(C) but not to ephrin receptor B2, another endogenous receptor for Aβ oligomers, suggesting that the drug's action is specific to the binding of Aβ oligomer to PrP(C) . Dextran on the other hand did not affect this binding. DSS also suppressed Aβ oligomer binding to cells expressing PrP(C) but not to control cells. Furthermore, while incubation of mouse hippocampal slices with Aβ oligomers inhibited the induction of long-term potentiation, simultaneous treatment with DSS restored the long-term potentiation. As DSS has already been approved for use in patients with hypertriglyceridemia, and its safety in humans has been confirmed, we propose further analysis of this drug as a candidate for AD treatment. Amyloid-β peptide (Aβ) oligomer-binding to cellular prion protein (PrP(C) ) is important in synaptic dysfunction in Alzheimer's disease (AD). We found here that dextran sulfate sodium (DSS) inhibits Aβ oligomer binding to PrP(C) . Simultaneous treatment of hippocampal slices with DSS restored long-term potentiation (LTP) in the presence of Aβ oligomers. Since DSS has already been approved for clinical use, we propose this drug is a candidate drug for AD treatment.

KEYWORDS:

Alzheimer's disease; amyloid beta; cellular prion protein; dextran sulfate sodium

PMID:
25963375
DOI:
10.1111/jnc.13166
[Indexed for MEDLINE]
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