title: Nanoparticle and other metal chelation therapeutics in Alzheimer disease.
abstract: Current therapies for Alzheimer disease (AD) such as the anticholinesterase inhibitors and the latest NMDA receptor inhibitor, Namenda, provide moderate symptomatic delay at various stages of disease, but do not arrest disease progression or supply meaningful remission. As such, new approaches to disease management are urgently needed. Although the etiology of AD is largely unknown, oxidative damage mediated by metals is likely a significant contributor since metals such as iron, aluminum, zinc, and copper are dysregulated and/or increased in AD brain tissue and create a pro-oxidative environment. This role of metal ion-induced free radical formation in AD makes chelation therapy an attractive means of dampening the oxidative stress burden in neurons. The chelator desferioxamine, FDA approved for iron overload, has shown some benefit in AD, but like many chelators, it has a host of adverse effects and substantial obstacles for tissue-specific targeting. Other chelators are under development and have shown various strengths and weaknesses. In this review, we propose a novel system of chelation therapy through the use of nanoparticles. Nanoparticles conjugated to chelators show a unique ability to cross the blood-brain barrier (BBB), chelate metals, and exit through the BBB with their corresponding complexed metal ions. This method may prove to be a safe and effective means of reducing the metal load in neural tissue thus staving off the harmful effects of oxidative damage and its sequelae.
authors.affiliation: Department of Radiology, University of Utah, Salt Lake City, UT 84102, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Garrett
authors.forename: Ping
authors.initials: P
authors.lastname: Men
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D001812:Blood-Brain Barrier / Q000378:metabolism; D002614:Chelating Agents / Q000378:metabolism / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000379:methods*; D006801:Humans; D049329:Nanostructures; D010539:Permeability
chemical_list: D002614:Chelating Agents