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An intracellular protein that binds amyloid-β peptide and mediates neurotoxicity in Alzheimer's disease

Abstract

Amyloid-β is a neurotoxic peptide which is implicated in the pathogenesis of Alzheimer's disease. It binds an intracellular polypeptide known as ERAB, thought to be a hydroxysteroid dehydrogenase enzyme, which is expressed in normal tissues, but is overexpressed in neurons affected in Alzheimer's disease. ERAB immunoprecipitates with amyloid-β, and when cell cultures are exposed to amyloid-β, ERAB inside the cell is rapidly redistributed to the plasma membrane. The toxic effect of amyloid-β on these cells is prevented by blocking ERAB and is enhanced by overexpression of ERAB. By interacting with intracellular amyloid-β, ERAB may therefore contribute to the neuronal dysfunction associated with Alzheimer's disease.

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Figure 1: Identification and cloning of a cell-associated binding protein for Aβ.
Figure 2: Expression of ERAB fusion protein: Aβ-binding properties.
Figure 3: Expression of ERAB in human tissue.
Figure 4: Expression of ERAB in cultured cells: localization to the endoplasmic reticulum and change in distribution following addition of Aβ.
Figure 5: ERAB contributes to Aβ-induced cytoxicity in neuroblastoma cells.
Figure 6: ERAB contributes to Aβ-induced cellular toxicity in ERAB-transfected COS cells.

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Acknowledgements

We thank G. C. Godman and G. Andres for help and advice during these studies and in preparation of the manuscript.

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Correspondence to Shi Du Yan.

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Du Yan, S., Fu, J., Soto, C. et al. An intracellular protein that binds amyloid-β peptide and mediates neurotoxicity in Alzheimer's disease. Nature 389, 689–695 (1997). https://doi.org/10.1038/39522

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