Abstract

The homeostasis of transition metal ions is central to many life processes, but the alterations in Fe, Zn, and Mn homeostasis are observed in the brain of patients of several neurodegenerative disorders. Abnormally high levels of non-transferrin-bound iron ions (NTBI), or labile iron ion, have been demonstrated in a number of neurodegenerative disorders including dementia, Parkinson’s disease (PD) and Alzheimer’s disease (AD), and oxidative stress closely related with NTBI in the brain is widely believed to be associated with neuronal death in these diseases. We have investigated the chemical mechanism of the abnormal accumulation of iron ions in the brain observed for the patients of neurodegenerative disorders, and based on these results we have prepared the new iron chelators, so-called super-polyphenols. Since our super-polyphenols can excrete only NTBI effectively from the plasma, not the iron in the holo-transferrin, our super polyphenols should be one of the most hopeful substances for labile iron removal therapy, including the prevention of dementia, Alzheimer’s and Parkinson’s diseases.  Our super-polyphenols are characterized by the following four points, i.e., 1) these super-polyphenols are water-insoluble, 2) these are not metabolized in the human body due to its insolubility in water and its polymeric structure (MW~90,000), 3) their iron (III) chelates are also water-insoluble, and 4) they do not interact with the iron ions in the holo-transferrin, and because of the these properties our super-polyphenols give no damage to human body.

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