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Methemoglobinemia—A biomarker and a link to ferric iron accumulation in Alzheimer’s disease

Advances in Bioscience and Biotechnology 2014年第1期5卷 12-18页

作者： Lucijan Mohorovic Anna M. Lavezzi Sanja Stifter George Perry djulija malatestinic Vladimir Micovic Eris Materljan Herman Haller Oleg Petrovic “Lino Rossi” Research Center Department of Biomedical Sur-gical and Dental Science University of Milan Milan Italy Department of Biology University of Texas at San Antonio San Antonio USA Department of Environmental Medicine University of Rijeka School of Medicine Rijeka Croatia Department of Family Medicine University of Rijeka School of Medicine Rijeka Croatia Department of Gynecology and Obstetrics University of Rijeka School of Medicine Rijeka Croatia Department of Pathology University of Rijeka School of Medi-cine Rijeka Croatia Department of Social Medicine and Epidemiology University of Rijeka School of Medicine Rijeka Croatia

Understanding the mechanism of oxidative stress is likely to yield new insights regarding the pathogenesis of Alzheimer’s disease (AD). Our earlier work focused on the difference between hemoglobin and methemoglobin degradation, respectively leading to ferrous (Fe2+) iron, or ferric (Fe3+) iron. Methemoglobin has the role of carrier, the donor of cytotoxic and redox-active ferric (Fe3+) iron, which can directly accumulate and increase the rate of capillary endothelial cell apoptosis, and may cross into the brain parenchyma, to the astrocytes, glia, neurons, and other neuronal cells (neurovascular unit). This supposition helps us to understand the transport and neuronal accumulation process of ferric iron, and determine how iron is transported and accumulated intracellularly, identifiable as “Brain rust”. Earlier research found that the incidences of neonatal jaundice (p = 0.034), heart murmur (p = 0.011) and disorders such as dyslalia and learning/memory impairments (p = 0.002) were significantly higher in those children born from mothers with methemoglobinemia. Our hypothesis suggests that prenatal iron abnormalities could lead to greater neuronal death, the disease ageing process, and neurodegenerative disorders such as AD and other neurodegenerative diseases.

关键词： Alzheimer’s Disease (AD) Apoptosis Blood-Brain Barrier (BBB) Brain Capillary Ferric Iron Deposition Hemoglobin and Methemoglobin Catabolism Neurodegenerative Brain Disease SIDS

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