Metal Chelators Coupled with Nanoparticles as Potential Therapeutic Agents for Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a devastating neuro-degenerative disorder characterized by the progressive and irreversible loss of memory followed by complete dementia. Despite the disease's high prevalence and great economic and social burden, an explicative etiology or viable cure is not available. Great effort has been made to better understand the disease's pathogenesis, and to develop more effective therapeutic agents. However, success is greatly hampered by the presence of the bloodbrain barrier that limits a large number of potential therapeutics from entering the brain. Nanoparticlemediated drug delivery is one of the few valuable tools for overcoming this impediment and its application as a potential AD treatment shows promise. In this review, the current studies on nanoparticle delivery of chelation agents as possible therapeutics for AD are discussed because several metals are found excessive in the AD brain and may play a role in the disease development. Specifically, a novel approach involving transport of iron chelation agents into and out of the brain by nanoparticles is highlighted. This approach may provide a safer and more effective means of simultaneously reducing several toxic metals in the AD brain. It may also provide insights into the mechanisms of AD pathophysiology, and prove useful in treating other iron-associated neurodegenerative diseases such as Friedreich's ataxia, Parkinson's disease, Huntington's disease and Hallervorden-Spatz Syndrome. It is important to note that the use of nanoparticle-mediated transport to facilitate toxicant excretion from diseased sites in the body may advance nanoparticle technology, which is currently focused on targeted drug delivery for disease prevention and treatment. The application of nanoparticle-mediated drug transport in the treatment of AD is at its very early stages of development and, therefore, more studies are warranted.

Zinc and the aging brain

“…However, the highest dose was well tolerated for 12 weeks and resulted in significantly lower cerebrospinal fluid Ab42 levels, and improved performance relative to baseline values on two executive function tests from the NTB (Faux et al 2010). While larger trials are required to further test the efficacy of PBT2, several novel compounds aimed at modulating zinc availability including targeted nanoparticles loaded with zinc or coupled to chelators are in the preclinical testing phase (Bush and Tanzi 2008;Liu et al 2009;Grabrucker et al 2011a).…”

Nanomedicine and Drug Delivery Strategies for Treatment of Genetic Diseases

“…This has been explored for delivery of nerve growth factor for Huntingon's disease (Kordower, et al, 1994). Nanocarriers have also been used as vehicles to assist in transporting chelating agents into the brain for iron capture and removal in Alzheimer's disease, also with potential in Huntington's and Parkinson's diseases (Liu, et al, 2009). Similar nanomedicine strategies can improve delivery of other small molecule therapies for genetic diseases, including hormones to control regulatory pathways, antibiotics, growth factors, cofactors, inhibitors or activators that act upstream or downstream of affected pathways, chaperones that favor proper protein folding, and other chemicals.…”

Pharmacological Approaches of Alzheimer's Disease: An Update

“…Transition metal chelator treatments in vivo and in vitro have shown promising results on the solubilization of A in logical function [18]. The current studies are focussing on nanoparticle delivery of chelation agents which can be possible treatment for AD [19]. Recently, a study was reported on lithium which shows decrease in both the production of A and tau phosphorylation and may improve memory on aluminium loaded rats [20].…”