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

Takahiro Aimi, Koichiro Suzuki, Tatsuya Hoshino, Tohru Mizushima

Research output: Contribution to journalArticle

8 Citations (Scopus)

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<sup>C</sup>) 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<sup>C</sup> 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<sup>C</sup> 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<sup>C</sup>. Dextran on the other hand did not affect this binding. DSS also suppressed Aβ oligomer binding to cells expressing PrP<sup>C</sup> 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.

Original languageEnglish
JournalJournal of Neurochemistry
DOIs
Publication statusAccepted/In press - 2015

Fingerprint

Dextran Sulfate
Oligomers
Amyloid
Alzheimer Disease
Long-Term Potentiation
Ephrin-B2
Eph Family Receptors
Medicine
PrPC Proteins
Hypertriglyceridemia
Dextrans
Pharmaceutical Preparations
Libraries
Prion Proteins
Prions
Safety
Assays
Cells
Therapeutics

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Cellular prion protein
  • Dextran sulfate sodium

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Dextran sulfate sodium inhibits amyloid-β oligomer binding to cellular prion protein. / Aimi, Takahiro; Suzuki, Koichiro; Hoshino, Tatsuya; Mizushima, Tohru.

In: Journal of Neurochemistry, 2015.

Research output: Contribution to journalArticle

Aimi, Takahiro ; Suzuki, Koichiro ; Hoshino, Tatsuya ; Mizushima, Tohru. / Dextran sulfate sodium inhibits amyloid-β oligomer binding to cellular prion protein. In: Journal of Neurochemistry. 2015.
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