Role of hydroxynonenal in membrane mediated amyloidogenesis by amyloid β proteins

BIOL 80

Liu Liu, lliu2@mail.med.upenn.edu1, Hiroaki Komatsu, hkomatsu@mail.med.upenn.edu1, Ian V. J. Murray, imurray@mail.med.upenn.edu2, and Paul H Axelsen3. (1) Department of Pharmacology, University of Pennsylvania, 105 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, (2) Center for Cancer Pharmacology, University of Pennsylvania, 849 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104, (3) Departments of Pharmacology, Biochemistry and Biophysics, and Medicine, the Johnson Foundation for Molecular Biophysics, University of Pennsylvania, Philadelphia, PA 19104
Oxidatively damaged lipid membranes are known to promote the aggregation of amyloid β proteins and fibril formation. In this report, the ability of hydroxynonenal to reproduce all of the previously observed effects of oxidative lipid damage on amyloid β proteins is demonstrated, and the mechanism by which it exerts these effects is examined using an array of biophysical methods. Results indicate that hydroxynonenal increases the affinity of amyloid β proteins for neutral lipid membranes, causing the protein to adopt a conformation on membranes that is similar to its conformation in a mature amyloid fibril, and creating nucleation sites for aggregation and fibril formation by unmodified Aβ. These findings suggest a specific mechanistic link between oxidative stress and a major histopathological feature of AD.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007