Bioinorganic Strategies to Study Multiple Facets in Dementia

Abstract

Alzheimer’s disease (AD), associated with degeneration of neurons and synapses in the brain, leads to motor impairment and eventual fatality. Neurodegeneration is related to interconnected features, including amyloid-β (Aβ) aggregate deposition, metal ion dyshomeostasis and miscompartmentalization, and inflammation and increased oxidative stress induced by overproducing reactive oxygen species (ROS). The interrelations between some of these pathological factors have been investigated. Metal ions are found in the Aβ plaque and contribute to Aβ-related toxicity and oxidative stress. ROS have been shown to increase Aβ aggregate generation. Our understanding of the correlation between these elements and AD pathology has been very limited, however. There is currently no cure for AD. To identify an effective cure, we require a better understanding of the relationship between various causative factors of this disease. Toward this goal, we need suitable chemical tools capable of targeting and regulating its multiple underlying factors simultaneously. In this presentation, the rational design and preparation of our chemical tools will be discussed with detailed molecular-level investigations of their interactions and reactivities with targets in vitro as well as their efficacies in vivo.