TITLE:
Methemoglobinemia—A biomarker and a link to ferric iron accumulation in Alzheimer’s disease
AUTHORS:
Lucijan Mohorovic, Anna M. Lavezzi, Sanja Stifter, George Perry, Djulija Malatestinic, Vladimir Micovic, Eris Materljan, Herman Haller, Oleg Petrovic
KEYWORDS:
Alzheimer’s Disease (AD); Apoptosis; Blood-Brain Barrier (BBB); Brain Capillary Ferric Iron Deposition; Hemoglobin and Methemoglobin Catabolism; Neurodegenerative Brain Disease; SIDS
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.5 No.1,
January
6,
2014
ABSTRACT: 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.