Chapter 5 - Development of iron chelator-nanoparticle conjugates as potential therapeutic agents for Alzheimer disease.

Oxidative stress is known to play a key role in the initiation and promotion of the neurodegeneration that characterizes the pathogenesis of Alzheimer disease (AD). An accumulation of redox active transition metals, including iron and copper, is likely a major generator of reactive oxidative species and other free radicals and is thought to induce a detrimental cycle of oxidative stress, amyloid-beta aggregation, and neurodegeneration. As such, metal chelators may provide an alternative therapeutic approach to sequester redox active metals and prevent the onslaught of oxidative damage. Unfortunately, however, metal chelation approaches are currently limited in their potential, since many cannot readily pass the blood-brain barrier (BBB), due to their hydrophilicity, and many are neurotoxic at high concentrations. To circumvent such issues, here we describe the development of iron chelator-nanoparticle conjugation that allows delivery of target chelator to the brain in the absence of neurotoxicity. Such nanoparticle delivery of iron chelators will likely provide a highly advantageous mode of attack on the oxidative stress that plagues AD as well as other conditions characterized by excess metal accumulation. Copyright 2009 Elsevier B.V. All rights reserved.