1.
Iron Dysregulation in Mitochondrial Dysfunction and Alzheimer's Disease.
Onukwufor, JO, Dirksen, RT, Wojtovich, AP
Antioxidants (Basel, Switzerland). 2022;11(4)
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Alzheimer’s disease (AD) is a progressive deterioration of the brain and memory, for which there is currently no cure. Important to the normal function of the brain is a tightly regulated iron supply and dysregulation in this process may be involved in the development of AD. This review paper aimed to determine how iron dysfunction is related to energy production in the brain and how a type of programmed cell death, that is controlled by iron, may be involved in the development of AD and targeted as a potential treatment. The paper reviewed how iron is regulated, with deficiency sensed by iron regulatory proteins (IRPs), which ultimately results in the release and transport of iron around the body and increased uptake in the diet. If these IRPs become impaired, then a dysregulation of iron levels can occur. Increases in brain iron levels have been associated with progressive development of AD and some areas of the brain are more susceptible than others especially the hippocampus, which is responsible for learning and memory. Increased iron levels in the brain maybe age dependent and associated with cognitive decline in individuals with AD. The mechanisms behind this were discussed and dysregulated iron alongside dysfunctional energy production has been observed in individuals with AD. There is some uncertainty on the causes of this, however it may involve the accumulation of iron which damages lipid membranes around the brain cells, causing them to die in a reaction known as ferroptosis. It was concluded that iron may have a pivotal role in the development of AD due to its importance for energy production and the prevention of brain cell death. This study could be used by healthcare professionals to understand that low iron levels may be involved in the development of AD and that checking and correcting any deficiencies may be of benefit.
Abstract
Alzheimer's disease (AD) is a devastating progressive neurodegenerative disease characterized by neuronal dysfunction, and decreased memory and cognitive function. Iron is critical for neuronal activity, neurotransmitter biosynthesis, and energy homeostasis. Iron accumulation occurs in AD and results in neuronal dysfunction through activation of multifactorial mechanisms. Mitochondria generate energy and iron is a key co-factor required for: (1) ATP production by the electron transport chain, (2) heme protein biosynthesis and (3) iron-sulfur cluster formation. Disruptions in iron homeostasis result in mitochondrial dysfunction and energetic failure. Ferroptosis, a non-apoptotic iron-dependent form of cell death mediated by uncontrolled accumulation of reactive oxygen species and lipid peroxidation, is associated with AD and other neurodegenerative diseases. AD pathogenesis is complex with multiple diverse interacting players including Aβ-plaque formation, phosphorylated tau, and redox stress. Unfortunately, clinical trials in AD based on targeting these canonical hallmarks have been largely unsuccessful. Here, we review evidence linking iron dysregulation to AD and the potential for targeting ferroptosis as a therapeutic intervention for AD.
2.
The Role of Iron in Brain Development: A Systematic Review.
McCann, S, Perapoch Amadó, M, Moore, SE
Nutrients. 2020;12(7)
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Iron deficiency is the most common vitamin or mineral deficiency worldwide and is particularly common among pregnant women, infants and young children due to high iron demands during periods of rapid growth. Iron plays an important role in the development of the brain, and animal studies suggest that getting enough iron in pregnancy and early childhood is particularly important. The aims of this systematic review were to (i) investigate the relationship between iron status and brain development and (ii) assess whether this relationship differs according to age or type of development (‘domain’). The researchers looked for studies on iron deficiency or iron supplementation in pregnancy and up to 4 years of age. 26 observational studies and 28 intervention studies were included in the review. There was no clear relationship between iron status and developmental outcomes across any of the ages or domains included. Many of the studies were of low quality and there was a wide variation in study design, along with a lack of research on pregnancy and early infancy. The researchers concluded that evidence for the impact of iron deficiency or iron supplementation on early development is inconsistent. Further high-quality research is needed, particularly within pregnancy and early infancy, which has previously been neglected.
Abstract
One-third of children falter in cognitive development by pre-school age. Iron plays an important role in many neurodevelopmental processes, and animal studies suggest that iron sufficiency in pregnancy and infancy is particularly important for neurodevelopment. However, it is not clear whether iron deficiency directly impacts developmental outcomes, and, if so, whether impact differs by timing of exposure or developmental domain. We searched four databases for studies on iron deficiency or iron supplementation in pregnancy, or at 0-6 months, 6-24 months, or 2-4 years of age. All studies included neurodevelopmental assessments in infants or children up to 4 years old. We then qualitatively synthesized the literature. There was no clear relationship between iron status and developmental outcomes across any of the time windows or domains included. We identified a large quantity of low-quality studies, significant heterogeneity in study design and a lack of research focused on pregnancy and early infancy. In summary, despite good mechanistic evidence for the role of iron in brain development, evidence for the impact of iron deficiency or iron supplementation on early development is inconsistent. Further high-quality research is needed, particularly within pregnancy and early infancy, which has previously been neglected.
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Low Zinc, Copper, and Manganese Intake is Associated with Depression and Anxiety Symptoms in the Japanese Working Population: Findings from the Eating Habit and Well-Being Study.
Nakamura, M, Miura, A, Nagahata, T, Shibata, Y, Okada, E, Ojima, T
Nutrients. 2019;11(4)
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Diet, as well as other lifestyle factors (sleep, exercise etc) are thought to play a significant role in the occurrence of mental disorders, including depression and anxiety. This study focused on the dietary intake of particular minerals (zinc, copper and manganese) and their effects on depression and anxiety of 2089 Japanese participants, each in full time employment. Reasons for the occurrence of mental disorders are considered multi-factorial, but insufficient mineral intake (particularly zinc) is believed to be a causal factor in the prevalence of depression and anxiety. Results of this cross-sectional study showed that low intake of zinc, copper and manganese was associated with depression and anxiety symptoms. More specifically, the effect of both low zinc and low copper intake indicated a higher susceptibility towards depression with both low and high manganese status, suggesting low zinc and copper intake contributes to depression and anxiety symptoms regardless of manganese status. Researchers acknowledge that more investigation is needed.
Abstract
Epidemiological studies have suggested that there is an association between diet and mental health. The aim of this study was to investigate the association between the intake of six minerals and mental disorders in a cross-sectional study. We used data from the Eating Habit and Well-being study in Japanese workers. Kessler's six-item psychological distress scale was used to detect mental disorders, with a cut-off score of 12/13, and a validated food frequency questionnaire was used to estimate dietary mineral intake. A total of 2089 participants with no history of depression were included. The prevalence of mental disorders was 6.9%. The lowest quartiles of zinc, copper, and manganese intakes were associated with mental disorders, whereas the lowest quartiles of calcium, magnesium, and iron intake were not associated with mental disorders. Combination analysis of high (≥median) or low (