Characterization of the interaction between Abeta 1-42 and glyceraldehyde phosphodehydrogenase.
Advances in the understanding of AD pathogenesis have recently provided strong support for a modified Abeta protein cascade hypothesis, stating that several different Abeta assemblies contribute to the triggering of a complex pathological cascade leading to neurodegeneration. Both in vitro and in vivo, Abeta rapidly forms fibrils (fAbeta), 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 fAbeta, we demonstrated that the GAPDH was specifically coprecipitated with fAbeta. The aim of this study was to characterize this interaction. First, it was shown by TEM that synthetic GAPDH directly binds fAbeta 1-42. Then rat synaptosomal proteins were purified and incubated with different forms of Abeta in various conditions, and the presence of GAPDH among the proteins coprecipitated with Abeta was studied by western blotting. Results showed that the interaction between GAPDH and fAbeta 1-42 is nonionic, as is not impaired by increasing salt concentrations. GAPDH is coprecipitated not only by fAbeta, but also by nonfibrillar forms of Abeta 1-42. The 41-42 Abeta sequence seems to be important in the interaction of GAPDH and Abeta, as more GAPDH was coprecipitated with fAbeta 1-42 than with fAbeta 1-40. GAPDH extracted from various subcellular fractions including mitochondria, was shown to interact with fAbeta. Our data demonstrate a direct interaction between Abeta and GAPDH and support the possibility that this interaction has an important pathogenic role in AD.
Verdier
Yann
Y
Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
Földi
István
I
Sergeant
Nicolas
N
Fülöp
Lívia
L
Penke
Zsuzsa
Z
Janáky
Tamás
T
Szücs
Mária
M
Penke
Botond
B
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013347:Subcellular Fractions / Q000201:enzymology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D005987:Glyceraldehyde-3-Phosphate Dehydrogenases