Journal article
Restored degradation of the Alzheimer's amyloid-β peptide by targeting amyloid formation
PJ Crouch, DJ Tew, T Du, DN Nguyen, A Caragounis, G Filiz, RE Blake, IA Trounce, CPW Soon, K Laughton, KA Perez, QX Li, RA Cherny, CL Masters, KJ Barnham, AR White
Journal of Neurochemistry | WILEY | Published : 2009
Abstract
Accumulation of neurotoxic amyloid-β (Aβ) is central to the pathology of Alzheimer's disease (AD). Elucidating the mechanisms of Aβ accumulation will therefore expedite the development of Aβ-targeting AD therapeutics. We examined activity of an Aβ-degrading protease (matrix metalloprotease 2) to investigate whether biochemical factors consistent with conditions in the AD brain contribute to Aβ accumulation by altering Aβ sensitivity to proteolytic degradation. An Aβ amino acid mutation found in familial AD, Aβ interactions with zinc (Zn), and increased Aβ hydrophobicity all strongly prevented Aβ degradation. Consistent to all of these factors is the promotion of specific Aβ aggregates where ..
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Awarded by National Health and Medical Research Council (NHMRC)
Awarded by University of Melbourne Early Career Researcher Grant Scheme
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council (NHMRC) through Program Grant 400202 to ARW, CLM, and KJB, and the University of Melbourne Early Career Researcher Grant Scheme (Project #500144) to PJC. ARW is a NHMRC RD Wright Fellow, KJB is a NHMRC Senior Research Fellow. SRCD was carried out with the support of the Daresbury Synchrotron Radiation Source and the assistance of David Clarke. Travel for DJT to perform SRCD work was funded by the Australian Nuclear Science and Technology Organisation through the Access to Major Resource Facilities Program. Electron microscopy was performed under the expert guidance of staff from the University of Melbourne Bio21 EM Unit.