Department of ChemistryAlzheimer???s Disease (AD), responsible for most dementia cases, is one of the prevalent neurodegenerative diseases. Multiple features (e.g., neuroinflammation, accumulation of amyloid aggregates, dyshomeostasis of metal ions) have been implicated in the pathogenesis of AD, and such multifactorial nature impedes the investigation of the effective treatment of the disease. To elucidate the unrevealed biological actions linked with the pathogenesis and identify the remedy for the disease, many studies have been focused on devising and utilizing small molecules as chemical probes or potential therapeutics. In Chapter 1, we describe the development of a small molecule, 1, as a chemical agent for understanding the interconnection between neuroinflammation and amyloid-?? (A??) peptides as well as a potential drug candidate against AD. By intervening in the inflammatory process of microglia, 1 could promote the microglial phagocytosis of A?? and subsequently ameliorates cognitive defects in vivo. These results could provide an advanced insight to future discovery of effective anti-neuroinflammatory drugs against neurodegeneration. In Chapter 2, a turn-on near-infrared (near-IR) fluorescent probe, 2, for imaging A?? aggregates is introduced. The ability of 2 was evaluated to alter fluorescent response depending on the degree of A?? aggregation, at the near-IR region, and its suitability for imaging A?? aggregates under cellular environments. This work allows us to attain new perceptions to devise improved fluorescent probes with better specificity and bioapplicability, via further structural modifications. In Chapter 3, the design of small molecules capable of detecting metal ions in living cells is described. These studies present the capability of our molecules to monitor metal ions in living cells. Overall, our studies illustrate the utilization of small molecules to gain a better understanding of the pathogenic factors of interest, which will contribute to invention of chemical agents used for elucidating the pathology of AD.clos
