Abstract
Iron is an essential trace metal for almost all organisms, including human; however, oxidative stress can easily be caused when iron is in excess, producing toxicity to the human body due to its capability to be both an electron donor and an electron acceptor. Although there is a strict regulation mechanism for iron homeostasis in the human body and brain, it is usually inevitably disturbed by genetic and environmental factors, or disordered with aging, which leads to iron metabolism diseases, including many neurodegenerative diseases such as Alzheimer’s disease (AD). AD is one of the most common degenerative diseases of the central nervous system (CNS) threatening human health. However, the precise pathogenesis of AD is still unclear, which seriously restricts the design of interventions and treatment drugs based on the pathogenesis of AD. Many studies have observed abnormal iron accumulation in different regions of the AD brain, resulting in cognitive, memory, motor and other nerve damages. Understanding the metabolic balance mechanism of iron in the brain is crucial for the treatment of AD, which would provide new cures for the disease. This paper reviews the recent progress in the relationship between iron and AD from the aspects of iron absorption in intestinal cells, storage and regulation of iron in cells and organs, especially for the regulation of iron homeostasis in the human brain and prospects the future directions for AD treatments.
Highlights
Oxidative stress can lead to neuronal damage; it has been observed that the disorder of iron metabolism and the expressional change in iron regulatory proteins in the iron metabolism pathway could lead to the accumulation of iron ions in the brain and induce oxidative stress, resulting in the damage of neurons [107]
Many experimental results have showed that iron accumulation in the brain of Alzheimer’s disease (AD) patients is one of the sources of brain oxidative stress, and this has a close relationship with the disorder of brain iron metabolism and some key iron homeostasis regulators, such as ferritin protein, transferrin protein, FPN, etc. [100]
When iron metabolism in the body is unbalanced, such reactive properties of iron may promote the generation of reactive oxygen species (ROS), which will lead to the excessive accumulation of iron ions in the body [155,156]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The transition metal element iron is the second most abundant metal element in the earth’s crust behind, aluminum It is an essential trace element and an important component of metalloprotein for human body [1,2]. More and more research teams on the pathogenesis of Alzheimer’s disease (AD) have shown that the oxidative stress induced by iron metabolism disorder and the production of ROS are related to the pathological process of AD [7,9]. This paper reviews the relevant research progress in the field of iron and AD in recent years, focusing on the oxidative stresses induced by normal iron metabolism and its metabolic disorders, especially for abnormal expression of the iron transporters, transferrin receptors, divalent metal transporters, and their relationships with the AD pathological mark proteins, such as Aβ and tau proteins. The iron homeostasis on AD provides a theoretical basis for the prevention and treatment of neurodegenerative diseases and an effective drug screening target
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