Alzheimer's disease (AD) is a neurodegenerative disorder that affects approximately 6 million people in North America. AD causes a loss of cognition and eventually leads to death. The dominant theory for AD is the Amyloid Hypothesis, postulating that amyloid-� (A�) plaques, or partially aggregated soluble A�, trigger a neurotoxic cascade causing AD pathology. High concentrations of metal ions, such as Cu(II) and Zn(II), have been found in A� plaques in the brain of AD patients. The formation of A� plaques, toxic oligomers, and reactive oxygen species (ROS) are related to the presence of these metals, especially redox-active Cu(II) and Fe(III). Oxidative stress caused by ROS in AD brain leads to cell death.A promising therapeutic approach is the use of metal-protein attenuating compounds (MPAC) for AD treatment. MPACs 8-hydroxiquinoline derivatives, such as PBT2, target the metal-A� interaction in the extracellular environment and normalize the distribution of metal ions and A� peptide in biological fluids. We have synthesized a series of 8-hydroxyquinoline Schiff-bases and evaluated their antioxidant potential and their effect on the process of aggregation of the A� peptide. We have shown that these compounds act as antioxidants, and in addition compete with the A� peptide for Cu ions restricting formation of toxic metal-containing oligomer species.

Development of 8-hydroxyquinoline derivatives as possible therapeutics for the treatment of Alzheimer's disease

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.