Iron As Therapeutic Targets In Human Diseases

Iron is an essential element for almost all organisms, a cofactor playing a crucial role in a number of vital functions, including oxygen transport, DNA synthesis, and respiration. However, its ability to exchange electrons renders excess iron potentially toxic, since it is capable of catalyzing the formation of highly poisonous free radicals. As a consequence, iron homeostasis is tightly controlled by sophisticated mechanisms that have been partially elucidated. Because of its biological importance, numerous disorders have been recently linked to the deregulation of iron homeostasis, which include not only the typical disorders of iron overload and deficiency but also cancer and neurodegenerative diseases. This leads iron metabolism to become an interesting therapeutic target for novel pharmacological treatments against these diseases. Several therapies are currently under development for hematological disorders, while other are being considered for different pathologies. The therapeutic targeting under study includes the hepcidin/ferroportin axis for the regulation of systemic iron homeostasis, complex cytosolic machineries for the regulation of the intracellular iron status and its association with oxidative damage, and reagents exploiting proteins of iron metabolism such as ferritin and transferrin receptor. A promising potential target is a recently described form of programmed cell death named ferroptosis, in which the role of iron is essential but not completely clarified. This Special Issue has the aim to summarize the state-of-the-art, and the latest findings published in the iron field, as well as to elucidate future directions.

Iron is an essential element for almost all organisms, a cofactor playing a crucial role in a number of vital functions, including oxygen transport, DNA synthesis, and respiration. However, its ability to exchange electrons renders excess iron potentially toxic, since it is capable of catalyzing the formation of highly poisonous free radicals. As a consequence, iron homeostasis is tightly controlled by sophisticated mechanisms that have been partially elucidated. Because of its biological importance, numerous disorders have been recently linked to the deregulation of iron homeostasis, which include not only the typical disorders of iron overload and deficiency but also cancer and neurodegenerative diseases. This leads iron metabolism to become an interesting therapeutic target for novel pharmacological treatments against these diseases. Several therapies are currently under development for hematological disorders, while other are being considered for different pathologies. The therapeutic targeting under study includes the hepcidin/ferroportin axis for the regulation of systemic iron homeostasis, complex cytosolic machineries for the regulation of the intracellular iron status and its association with oxidative damage, and reagents exploiting proteins of iron metabolism such as ferritin and transferrin receptor. A promising potential target is a recently described form of programmed cell death named ferroptosis, in which the role of iron is essential but not completely clarified. This Special Issue has the aim to summarize the state-of-the-art, and the latest findings published in the iron field, as well as to elucidate future directions.

Iron is an essential element for almost all organisms, a cofactor playing a crucial role in a number of vital functions, including oxygen transport, DNA synthesis, and respiration. However, its ability to exchange electrons renders excess iron potentially toxic, since it is capable of catalyzing the formation of highly poisonous free radicals. As a consequence, iron homeostasis is tightly controlled by sophisticated mechanisms that have been partially elucidated. Because of its biological importance, numerous disorders have been recently linked to the deregulation of iron homeostasis, which include not only the typical disorders of iron overload and deficiency but also cancer and neurodegenerative diseases. This leads iron metabolism to become an interesting therapeutic target for novel pharmacological treatments against these diseases. Several therapies are currently under development for hematological disorders, while other are being considered for different pathologies. The therapeutic targeting under study includes the hepcidin/ferroportin axis for the regulation of systemic iron homeostasis, complex cytosolic machineries for the regulation of the intracellular iron status and its association with oxidative damage, and reagents exploiting proteins of iron metabolism such as ferritin and transferrin receptor. A promising potential target is a recently described form of programmed cell death named ferroptosis, in which the role of iron is essential but not completely clarified. This Special Issue has the aim to summarize the state-of-the-art, and the latest findings published in the iron field, as well as to elucidate future directions.

Iron is an essential element for almost all organisms, a cofactor playing a crucial role in a number of vital functions, including oxygen transport, DNA synthesis, and respiration. However, its ability to exchange electrons renders excess iron potentially toxic, since it is capable of catalyzing the formation of highly poisonous free radicals. As a consequence, iron homeostasis is tightly controlled by sophisticated mechanisms that have been partially elucidated. Because of its biological importance, numerous disorders have been recently linked to the deregulation of iron homeostasis, which include not only the typical disorders of iron overload and deficiency but also cancer and neurodegenerative diseases. This leads iron metabolism to become an interesting therapeutic target for novel pharmacological treatments against these diseases. Several therapies are currently under development for hematological disorders, while other are being considered for different pathologies. The therapeutic targeting under study includes the hepcidin/ferroportin axis for the regulation of systemic iron homeostasis, complex cytosolic machineries for the regulation of the intracellular iron status and its association with oxidative damage, and reagents exploiting proteins of iron metabolism such as ferritin and transferrin receptor. A promising potential target is a recently described form of programmed cell death named ferroptosis, in which the role of iron is essential but not completely clarified. This Special Issue has the aim to summarize the state-of-the-art, and the latest findings published in the iron field, as well as to elucidate future directions.

"Iron and Human Disease is the first book to cover the three key aspects of human iron metabolism: the accumulation of iron in adults, iron as a limiting factor for tumor and infectious cell growth, and iron as a catalyst for oxygen free radical production. The book describes the hypotheses and findings related to the role of iron in cardiovascular disease (including reperfusion injury), cancer, aging, and autoimmune and neurodegenerative diseases. Other topics covered include the molecular biology and biochemistry of iron, the general principles governing iron balance, iron in the immune system and acute phase response, and new preventive and therapeutic strategies. Iron and Human Disease will be a useful reference for biomedical investigators, physicians, nutritionists, and public health officials."--Provided by publisher.

This volume is the newest release in the authoritative series issued by the National Academy of Sciences on dietary reference intakes (DRIs). This series provides recommended intakes, such as Recommended Dietary Allowances (RDAs), for use in planning nutritionally adequate diets for individuals based on age and gender. In addition, a new reference intake, the Tolerable Upper Intake Level (UL), has also been established to assist an individual in knowing how much is "too much" of a nutrient. Based on the Institute of Medicine's review of the scientific literature regarding dietary micronutrients, recommendations have been formulated regarding vitamins A and K, iron, iodine, chromium, copper, manganese, molybdenum, zinc, and other potentially beneficial trace elements such as boron to determine the roles, if any, they play in health. The book also: Reviews selected components of food that may influence the bioavailability of these compounds. Develops estimates of dietary intake of these compounds that are compatible with good nutrition throughout the life span and that may decrease risk of chronic disease where data indicate they play a role. Determines Tolerable Upper Intake levels for each nutrient reviewed where adequate scientific data are available in specific population subgroups. Identifies research needed to improve knowledge of the role of these micronutrients in human health. This book will be important to professionals in nutrition research and education.

The world continues to lose more than a million lives each year to the HIV epidemic, and nearly two million individuals were infected with HIV in 2017 alone. The new Sustainable Development Goals, adopted by countries of the United Nations in September 2015, include a commitment to end the AIDS epidemic by 2030. Considerable emphasis on prevention of new infections and treatment of those living with HIV will be needed to make this goal achievable. With nearly 37 million people now living with HIV, it is a communicable disease that behaves like a noncommunicable disease. Nutritional management is integral to comprehensive HIV care and treatment. Improved nutritional status and weight gain can increase recovery and strength of individuals living with HIV/AIDS, improve dietary diversity and caloric intake, and improve quality of life. This book highlights evidence-based research linking nutrition and HIV and identifies research gaps to inform the development of guidelines and policies for the United Nations’ Sustainable Development Goals. A comprehensive approach that includes nutritional interventions is likely to maximize the benefit of antiretroviral therapy in preventing HIV disease progression and other adverse outcomes in HIV-infected men and women. Modification of nutritional status has been shown to enhance the quality of life of those suffering HIV/AIDS, both physically in terms of improved body mass index and immunological markers, and psychologically, by improving symptoms of depression. While the primary focus for those infected should remain on antiretroviral treatment and increasing its availability and coverage, improvement of nutritional status plays a complementary role in the management of HIV infection.

Within the last few years, iron research has yielded exciting new insights into the under standing of normal iron homeostasis. However, normal iron physiology offers little protec tion from the toxic effects of pathological iron accumulation, because nature did not equip us with effective mechanisms of iron excretion. Excess iron may be effectively removed by phlebotomy in hereditary hemochromatosis, but this method cannot be applied to chronic anemias associated with iron overload. In these diseases, iron chelating therapy is the only method available for preventing early death caused mainly by myocardial and hepatic iron toxicity. Iron chelating therapy has changed the quality of life and life expectancy of thalassemic patients. However, the high cost and rigorous requirements of deferoxamine therapy, and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. Such development, and the evolution of improved strategies of iron chelating therapy require better understanding of the pathophysiology of iron toxicity and the mechanism of action of iron chelating drugs. The timeliness of the present volume is underlined by several significant develop ments in recent years. New insights have been gained into the molecular basis of aberrant iron handling in hereditary disorders and the pathophysiology of iron overload (Chapters 1-5).