Human Nck-associated protein 1 and its binding protein affect the metabolism of beta-amyloid precursor protein with Swedish mutation

Neurosci Lett. 2001 Dec 4;316(1):50-4. doi: 10.1016/s0304-3940(01)02370-9.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system, and beta-amyloid precursor protein (betaAPP) plays a pivotal role in AD pathology. We previously reported that the suppression of human Nck-associated protein 1 (Nap1) whose expression was down-regulated in sporadic AD led to apoptosis in human neuroblastoma cells, and also its binding protein, hNap1BP was identified. Here, we examined whether these molecules were involved in the regulation of betaAPP metabolism. Human Nap1 and hNap1BP were found not to effect the amount of intracellular betaAPP but induced sAPPalpha secretion. Interestingly, they didn't reduce but slightly increased the extracellular level of Abeta. Furthermore, neither human Nap1 nor hNap1BP influenced the ratio of Abeta42/43 to total Abeta. Taken together, human Nap1 and hNap1BP may play a role in regulation of beta-secretase activity in the processing of betaAPP.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Carrier Proteins / physiology*
  • Cell Cycle Proteins / physiology*
  • Cell Line
  • DNA-Binding Proteins / physiology*
  • Humans
  • Mutation*

Substances

  • Adaptor Proteins, Signal Transducing
  • Amyloid beta-Protein Precursor
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • NCKAP1 protein, human