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Ironjustic
Tue, Dec-18-07, 17:15
Blat D, Weiner L, Youdim MB, Fridkin M A Novel Iron-Chelating
Derivative of the Neuroprotective Peptide NAPVSIPQ Shows
Superior Antioxidant and Antineurodegenerative Capabilities.
[JOURNAL ARTICLE] J Med Chem 2007 Dec 14.

Affecting an estimated 5% of adults over 65 years of age,
Parkinson's disease and Alzheimer's disease are the most
common neurodegenerative disorders. Accumulating evidence
suggests that oxidative stress induced by the breakdown of
iron homeostasis is a major contributor to the neuronal loss
observed in neurodegeneration. Thus, brain-permeable iron
chelators may present potential therapeutic benefits. In the
present study, iron-chelating hydroxamate groups were
introduced into the NAP (NAPVSIPQ) peptide, whose
neuroprotective qualities have been widely demonstrated. Our
experiments revealed that the novel dihydroxamate peptide 3 is
capable of inhibiting iron-catalyzed hydroxyl radical
formation and lipid peroxidation, abilities that are not part
of the repertoire of its parent peptide. In addition, peptide
3 was superior to native NAP in protecting human neuroblastoma
cell cultures against the toxicity of hydrogen peroxide. These
results suggest that NAP-based iron chelators deserve further
investigation in the search for drug candidates for
neurodegeneration.
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