beta -Amyloid peptide-induced apoptosis regulated by a novel protein containing a g protein activation module

  • J Biol Chem. 2001 Jun 1;276(22):18748-56. doi: 10.1074/jbc.M011161200.
E M Kajkowski  1 ,  C F Lo ,  X Ning ,  S Walker ,  H J Sofia ,  W Wang ,  W Edris ,  P Chanda ,  E Wagner ,  S Vile ,  K Ryan ,  B McHendry-Rinde ,  S C Smith ,  A Wood ,  K J Rhodes ,  J D Kennedy ,  J Bard ,  J S Jacobsen ,  B A Ozenberger
Affiliations
  • 1. Wyeth Neuroscience, Wyeth-Ayerst Research, CN 8000, Princeton, New Jersey 08543-8000, USA.
PMID: 11278849 DOI: 10.1074/jbc.M011161200
Abstract

Degeneration of neurons in Alzheimer's Disease is mediated by beta-amyloid peptide by diverse mechanisms, which include a putative apoptotic component stimulated by unidentified signaling events. This report describes a novel beta-amyloid peptide-binding protein (denoted BBP) containing a G protein-coupling module. BBP is one member of a family of three proteins containing this conserved structure. The BBP subtype bound human beta-amyloid peptide in vitro with high affinity and specificity. Expression of BBP in Cell Culture induced caspase-dependent vulnerability to beta-amyloid peptide toxicity. Expression of a signaling-deficient dominant negative BBP mutant suppressed sensitivity of human Ntera-2 neurons to beta-amyloid peptide mediated toxicity. These findings suggest that BBP is a target of neurotoxic beta-amyloid peptide and provide new insight into the molecular pathophysiology of Alzheimer's Disease.