Iron chelation / efficacy in parkinsons disease

Discussion in 'Food and nutrition' started by [email protected], Mar 20, 2005.

  1. Med Hypotheses. 2005;64(4):736-41. Related Articles, Links


    Pharmacological manipulation of ataxia-telangiectasia kinase activity
    as a treatment for Parkinson's disease.

    Edwin Shackelford R, Manuszak RP, Heard SC, Link CJ, Wang S.

    Department of Pathology, Lousiana State University at Shreveport, 1501
    Kings Hwy, P.O. Box 33932, Shreveport, LA 711030-3932, USA.

    Parkinson's disease (PD) is a major cause of morbidity and mortality
    among older individuals. Although the causes of Parkinson's disease are
    multifactorial, considerable evidence indicates that elevated labile
    iron in the substantia nigra pars compacta plays an important role in
    producing oxyradicals which subsequently damage nigro-striatal neurons.
    Based on this several researchers have suggested that blood-brain
    barrier crossing iron chelators might have clinical efficacy in
    treating PD. Work demonstrating that iron chelators protect
    nigro-striatal neurons in the
    N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and
    6-hydroxydopamine-induced rodent PD models supports this hypothesis.
    Recently, we found that the ATM gene product (mutated in
    ataxia-telangiectasia, A-T), is required for cell survival and genomic
    stability maintenance following exposure to low labile iron
    concentrations. Iron chelators (desferal, quercetin, and apoferritin)
    also increase A-T cell genomic stability and viability, and activate
    ATM-dependent cellular events in normal cells. Additionally
    Atm-deficient mice exhibit a selective loss of dopaminergic
    nigro-striatal neurons. Based on this, we propose that iron chelators
    protect the substantia nigra pars compacta not only by chelating labile
    iron and reducing oxyradical formation, but also by inducing ATM
    activity, leading to increased oxidative stress resistance and DNA
    repair. Support for this hypothesis comes from the recent observation
    that the iron chelating flavonoid quercetin both directly activates ATM
    and protects neuronal cells from the toxic effects of the
    N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Therefore since; (1) ATM
    is required for iron toxicity resistance, (2) iron chelators such as
    quercetin, desferal, and apoferritin induce ATM activity and/or
    ATM-dependent events, and (3), Atm-deficient mice preferentially lose
    dopaminergic nigro-striatal neurons, we propose that ATM activity has
    an important function in PD. Furthermore, pharmacological manipulation
    of ATM activity via iron chelation might have clinical efficacy in PD
    treatment.

    PMID: 15694690 [PubMed - in process]

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