. 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.

    References:

    . Evidence for oxidative stress in Pick disease and corticobasal degeneration. Brain Res. 1995 Oct 23;696(1-2):268-71. PubMed.

    . Sequestration of iron by Lewy bodies in Parkinson's disease. Acta Neuropathol. 2000 Aug;100(2):111-4. PubMed.

    . A histochemical study of iron, transferrin, and ferritin in Alzheimer's diseased brains. J Neurosci Res. 1992 Jan;31(1):75-83. PubMed.

    . Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease. J Neurosci Res. 1992 Feb;31(2):327-35. PubMed.

    . 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.

    . Nanoparticle and other metal chelation therapeutics in Alzheimer disease. Biochim Biophys Acta. 2005 Sep 25;1741(3):246-52. PubMed.

    . Nanoparticle iron chelators: a new therapeutic approach in Alzheimer disease and other neurologic disorders associated with trace metal imbalance. Neurosci Lett. 2006 Oct 9;406(3):189-93. PubMed.

    . Metal chelators coupled with nanoparticles as potential therapeutic agents for Alzheimer's disease. J Nanoneurosci. 2009 Jun 1;1(1):42-55. PubMed.

    . Desferrioxamine and Alzheimer's disease: video home behavior assessment of clinical course and measures of brain aluminum. Ther Drug Monit. 1993 Dec;15(6):602-7. PubMed.

    . Redox metals and oxidative abnormalities in human prion diseases. Acta Neuropathol. 2005 Sep;110(3):232-8. PubMed.

    . In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: a central role for bound transition metals. J Neurochem. 2000 Jan;74(1):270-9. PubMed.

    . Expression of heme oxygenase-1 in the senescent and Alzheimer-diseased brain. Ann Neurol. 1995 Jun;37(6):758-68. PubMed.

    . Oxidative stress and iron imbalance in Alzheimer disease: how rust became the fuss!. J Alzheimers Dis. 2006;9(3 Suppl):305-8. PubMed.

    . Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9866-8. PubMed.

    . Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. Am J Pathol. 1994 Jul;145(1):42-7. PubMed.

    . Abnormal localization of iron regulatory protein in Alzheimer's disease. Brain Res. 1998 Mar 30;788(1-2):232-6. PubMed.

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