. Dysregulation of iron homeostasis in the CNS contributes to disease progression in a mouse model of amyotrophic lateral sclerosis. J Neurosci. 2009 Jan 21;29(3):610-9. PubMed.

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  1. Comment by Gang Liu, Xiongwei Zhu, Barney Dwyer, Rudy J. Castellani, Hyoung-gon Lee, George Perry, Mark A. Smith

    Chelation and Neurodegenerative Diseases: Nanoparticles as Proof of Concept
    The notion that iron dyshomeostasis contributes to the pathogenesis of a number of neurodegenerative disorders, now including amyotrophic lateral sclerosis (Jeong et al., 2009), is well established (Castellani et al., 1995; Smith et al., 1997; Castellani et al., 2000; Sayre et al., 2000; Petersen et al., 2005; Smith, 2006). In parallel, changes in a number of iron homeostasis proteins are also altered, including heme oxygenase-1 (Smith et al., 1994; Schipper et al., 1995), ferritin (Connor et al., 1992), and iron regulatory proteins (Connor et al., 1992; Smith et al., 1998).

    While clinical trials in neurodegenerative diseases using chelation therapy have been limited, such an approach has shown promise (McLachlan et al., 1993). Unfortunately, limited blood-brain barrier permeability and/or cytotoxicity with resultant side effects have limited the interpretation of such trials. In contrast to existing chelators, we recently developed a novel nanoparticle-chelator conjugate that shows potential for allowing free passage into and out of the brain without changing chelation properties (Liu et al., 2005; Liu et al., 2006; Liu et al., 2009). While still at a preclinical stage of development, the utility of such nanoparticle conjugates obviously merits serious consideration for future clinical trials to evaluate the potential of this strategy for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis.

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