Metal complexing agents as therapies for Alzheimer's disease

Abstract

Modern research approaches into drug development for Alzheimer's disease (AD) target β-amyloid (Aβ) accumulation in the brain. The main approaches attempt to prevent Aβ production (secretase inhibitors) or to clear Aβ (vaccine). However, there is now compelling evidence that Aβ does not spontaneously aggregate, but that there is an age-dependent reaction with excess brain metal (copper, iron and zinc), which induces the protein to precipitate into metal-enriched masses (plaques). The abnormal combination of Aβ with Cu or Fe induces the production of hydrogen peroxide, which may mediate the conspicuous oxidative damage to the brain in AD. We have developed metal-binding compounds that inhibit..