Methemoglobinemia as biomarker and precursor of brain capillary oxidative damage link to ferric iron accumulation and originator of neurodegenerative disease
2017
Our main aim is to make a contribution to the establishment of sources of oxidants as the key factors in understanding the role that oxidants and oxidative stress play in the pathogenesis of neurodegeneration, i.e. in the progression of Alzheimer’s disease (AD). Our original observation pointed out the main difference between the hemoglobin and methemoglobin degradation, did from the heme oxygenation when a hemoglobin results in ferrous (Fe2+) iron, but methemoglobin catabolism produces ferric (Fe3+) iron. The methemoglobin plays a role of the carrier, the donor of cytotoxic and redox- active ferric (Fe3+) iron, and it also acts as the originator of neurodegenerative diseases. The abundant and permanent source of redox- active ferric (Fe3+) iron which, without Ferrous-Ferric inversions, has “in situ” direct impact on endothelial small vessels in the brain accumulates and increases the rate of capillary endothelial cell apoptosis and possibly crosses into brain parenchyma to the astrocytes, glia, neurons, and other neuronal cells. Our understanding of the transport and neuronal accumulation of ferric (Fe3+) iron points to how microvessels are organized into a well-structured neurovascular unit with harmful consequences to the brain. Our previously conducted research found that the neonatal jaundice incidence (p=0.034), heart murmur at a later age (p=0.011) and mild disorders in children and adults such as dyslalia and learning/memory impairments (p=0.002) were significantly higher than in children and adults of control mothers without pregnancy methemoglobinemia. The consequence are performed as initial brain iron harmful effects from the mother-fetal pregnancy methemoglobinemia complication, and according to our hypothesis in humans could be followed with the neuronal death, the disease aging process, and leading finally to the severe disorders as AD, PD and other neurodegenerative diseases.
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