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

Nature. 1997 Oct 16;389(6652):689-95. doi: 10.1038/39522.

Abstract

Amyloid-beta 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-beta, and when cell cultures are exposed to amyloid-beta, ERAB inside the cell is rapidly redistributed to the plasma membrane. The toxic effect of amyloid-beta on these cells is prevented by blocking ERAB and is enhanced by overexpression of ERAB. By interacting with intracellular amyloid-beta, ERAB may therefore contribute to the neuronal dysfunction associated with Alzheimer's disease.

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • COS Cells
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cloning, Molecular
  • HeLa Cells
  • Humans
  • Hydroxysteroid Dehydrogenases / genetics
  • Hydroxysteroid Dehydrogenases / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transfection

Substances

  • Amyloid beta-Peptides
  • Carrier Proteins
  • Recombinant Fusion Proteins
  • Hydroxysteroid Dehydrogenases
  • 3-Hydroxyacyl CoA Dehydrogenases
  • HSD17B10 protein, human
  • Hsd17b10 protein, mouse

Associated data

  • GENBANK/U96132