Minding metals: tailoring multifunctional chelating agents for neurodegenerative disease.
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Neurodegenerative diseases like Alzheimer's and Parkinson's disease are associated with elevated levels of iron, copper, and zinc and consequentially high levels of oxidative stress. Given the multifactorial nature of these diseases, it is becoming evident that the next generation of therapies must have multiple functions to combat multiple mechanisms of disease progression. Metal-chelating agents provide one such function as an intervention for ameliorating metal-associated damage in degenerative diseases. Targeting chelators to adjust localized metal imbalances in the brain, however, presents significant challenges. In this perspective, we focus on some noteworthy advances in the area of multifunctional metal chelators as potential therapeutic agents for neurodegenerative diseases. In addition to metal chelating ability, these agents also contain features designed to improve their uptake across the blood-brain barrier, increase their selectivity for metals in damage-prone environments, increase antioxidant capabilities, lower Abeta peptide aggregation, or inhibit disease-associated enzymes such as monoamine oxidase and acetylcholinesterase.
Published Version (Please cite this version)10.1039/b919237a
Publication InfoPerez, Lissette R; & Franz, Katherine J (2010). Minding metals: tailoring multifunctional chelating agents for neurodegenerative disease. Dalton Trans, 39(9). pp. 2177-2187. 10.1039/b919237a. Retrieved from https://hdl.handle.net/10161/4119.
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Member of the Duke Cancer Institute
Research in the Franz group is involved in elucidating the structural and functional consequences of metal ion coordination in biological systems. We are particularly interested in understanding the coordination chemistry utilized by biology to manage essential yet toxic species like copper and iron. Understanding these principles further guides our development of new chemical tools to manipulate biological metal ion location, speciation, and reactivity for potential therapeutic benefit. We use