Characterization of the interaction between Aβ 1-42 and glyceraldehyde phosphodehydrogenase

Yann Verdier, István Földi, Nicolas Sergeant, Lívia Fülöp, Zsüzs Penke, Tamás Janáky, Mária Szücs, Botond Penke

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Advances in the understanding of AD pathogenesis have recently provided strong support for a modified Aβ protein cascade hypothesis, stating that several different Aβ assemblies contribute to the triggering of a complex pathological cascade leading to neurodegeneration. Both in vitro and in vivo, Aβ rapidly forms fibrils (fAβ), which are able to interact with various molecular partners, including proteins, lipids and proteoglycans. In a previous study aimed to identify some of these molecular partners of fAβ, we demonstrated that the GAPDH was specifically coprecipitated with fAβ. The aim of this study was to characterize this interaction. First, it was shown by TEM that synthetic GAPDH directly binds fAβ 1-42. Then rat synaptosomal proteins were purified and incubated with different forms of Aβ in various conditions, and the presence of GAPDH among the proteins coprecipitated with Aβ was studied by western blotting. Results showed that the interaction between GAPDH and fAβ 1-42 is nonionic, as is not impaired by increasing salt concentrations. GAPDH is coprecipitated not only by fAβ, but also by nonfibrillar forms of Aβ 1-42. The 41-42 Aβ sequence seems to be important in the interaction of GAPDH and Aβ, as more GAPDH was coprecipitated with fAβ 1-42 than with fAβ 1-40. GAPDH extracted from various subcellular fractions including mitochondria, was shown to interact with fAβ. Our data demonstrate a direct interaction between Aβ and GAPDH and support the possibility that this interaction has an important pathogenic role in AD.

Original languageEnglish
Pages (from-to)755-762
Number of pages8
JournalJournal of Peptide Science
Volume14
Issue number6
DOIs
Publication statusPublished - Jun 1 2008

    Fingerprint

Keywords

  • Alzheimer's disease
  • Beta-amyloid peptide
  • Binding protein
  • Coprecipitation assay
  • GAPDH

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this