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

• 作者: Anna M. Lavezzi Djulija Malatestinic Eris Materljan George Perry Herman Haller Lucijan Mohorovic Oleg Petrovic Sanja Stifter Vladimir Micovic
• 来源期刊: 生命科学与技术进展(英文)
• 学科: 医学
• 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
• 年，卷（期）: 2014,（1）
• 页码范围: 12-18
• 页数: 7页
• 分类号: R73

摘要

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.