Characterization of the interaction between Aβ 1–42 and glyceraldehyde phosphodehydrogenase |
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Authors: | Yann Verdier István Földi Nicolas Sergeant Lívia Fülöp Zsuzsa Penke Tamás Janáky Mária Szücs Botond Penke |
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Affiliation: | 1. Department of Medical Chemistry, University of Szeged, Dóm tér 8, H‐6720 Szeged, Hungary;2. Ecole Superieure de Physique et de Chimie Industrielles de la ville Paris (ESPCI‐Paris Tech), CNRS/ESPCI UMR 7637 ‐ Neurobiology and Cellular Diversity, 10, rue Vauquelin, F‐75005 Paris, France;3. INSERM U815, Centre Jean‐Pierre Aubert, Neurodegenerative Disorders and Neuronal Death, 1, Place de Verdun, F‐59045 Lille, France;4. Department of Comparative Physiology, University of Szeged, H‐6701, Szeged, Hungary;5. Neurobiology of Learning, Memory and Communication, UMR 8620, CNRS, Univ Paris Sud, 91405 Orsay, France;6. Supramolecular and Nanostructured Materials Research Group of Hungarian Academy of Sciences, Dóm tér 8, H‐6725 Szeged, Hungary;7. Institute of Biochemistry, Biological Research Center, H‐6701 Szeged, Hungary |
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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. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. |
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Keywords: | beta‐amyloid peptide binding protein GAPDH coprecipitation assay Alzheimer's disease |
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