Wednesday, November 4, 2009
Ballroom A+B (Camino Real Hotel)
Misfolded proteins, and the associated endoplasmic reticulum (ER) stress, are emerging as hallmarks of age- and neurodegeneration-related disorders such as Huntington’s disease (HD), Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis. Recent and compelling evidence has linked nitrosative stress and the ER-resident oxidoreductase, protein disulfide isomerase (PDI), to the pathogenesis of PD and AD. Overexpression of PDI has been found to reduce the formation of polyubiquitinated proteins, making the oxidoreductase an important target for therapeutic intervention in PD, AD and other age- and neurodegeneration-related disorders. We demonstrate the NO-scavenging ability of the biphenolic natural products curcumin and masoprocol and the concomitant prevention of S-nitrosylation of PDI by a model NO-donor. Furthermore, both ethnopharmaceuticals accelerate protein fold acquisition in their neat and nitrated forms, making them attractive candidates for prevention of age- and neurodegeneration-related diseases.