Generation of amyloid beta peptide with pyroglutamate at position 3 in primary cortical neurons

Neurosci Lett. 2002 Jul 12;327(1):25-8. doi: 10.1016/s0304-3940(02)00351-8.

Abstract

The majority of amyloid beta peptide (Abeta) deposited in the brains of Alzheimer's disease (AD) patients is N-truncated, especially Abeta starting with pyroglutamate at position 3 (Abeta(3(pE))). To develop a system in which Abeta(3(pE)) is generated in primary neurons and to clarify the cyclization mechanism of N-terminal glutamate, we constructed amyloid precursor protein complementary DNAs which encoded a potential precursor for Abeta(3(pE)) by amino acid substitution and deletion. Among them, expression of NLQ construct by Sindbis virus resulted in secretion of Abeta(3(pE)) from primary neurons, whereas the N-termini of Abeta derived from NL and NLE constructs were intact. Therefore, the NLQ construct would be useful in establishing an animal model which produces Abeta(3(pE)).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Amyloid beta-Peptides / biosynthesis*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cell Survival
  • Cells, Cultured
  • DNA, Complementary
  • Gene Deletion
  • Gene Expression
  • Humans
  • Mass Spectrometry
  • Mice
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Neurons / cytology
  • Neurons / metabolism*
  • Pyrrolidonecarboxylic Acid / metabolism*
  • Sindbis Virus / genetics

Substances

  • Amyloid beta-Peptides
  • DNA, Complementary
  • Pyrrolidonecarboxylic Acid