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

Amyloid- peptide (A), 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 A oligomer to cellular prion protein (PrPC) plays an important role in synaptic dysfunction in a mouse model of AD. Here, we have screened for compounds that inhibit A oligomer binding to PrPC 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 A oligomer binding to PrPC but not to ephrin receptor B2, another endogenous receptor for A oligomers, suggesting that the drug's action is specific to the binding of A oligomer to PrPC. Dextran on the other hand did not affect this binding. DSS also suppressed A oligomer binding to cells expressing PrPC but not to control cells. Furthermore, while incubation of mouse hippocampal slices with A 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.