Abstract
Iron is an essential element that participates in numerous cellular processes. Any disruption of iron homeostasis leads to either iron deficiency or iron overload, which can be detrimental for humans’ health, especially in elderly. Each of these changes contributes to the faster development of many neurological disorders or stimulates progression of already present diseases. Age-related cellular and molecular alterations in iron metabolism can also lead to iron dyshomeostasis and deposition. Iron deposits can contribute to the development of inflammation, abnormal protein aggregation, and degeneration in the central nervous system (CNS), leading to the progressive decline in cognitive processes, contributing to pathophysiology of stroke and dysfunctions of body metabolism. Besides, since iron plays an important role in both neuroprotection and neurodegeneration, dietary iron homeostasis should be considered with caution. Recently, there has been increased interest in sex-related differences in iron metabolism and iron homeostasis. These differences have not yet been fully elucidated. In this review we will discuss the latest discoveries in iron metabolism, age-related changes, along with the sex differences in iron content in serum and brain, within the healthy aging population and in neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke.
Highlights
Iron is an essential micronutrient because of its importance in the process of erythropoiesis, oxidative metabolism, and cellular immune responses [1]
Hepcidin transcription is regulated by bone morphogenic protein 6 (BMP6) [85], which acts on hepatocytes through BMP receptor (BMPR) [86]
Brain iron accumulation is considered as a hallmark of aging [146] and it is associated with the progressive imbalance between antioxidant defenses and intracellular generation of reactive oxygen species (ROS) [147]
Summary
Iron is an essential micronutrient because of its importance in the process of erythropoiesis, oxidative metabolism, and cellular immune responses [1]. An increased number of recent experimental and clinical discoveries about the sex-related differences in iron metabolism present in certain neurological disorders [16,17,18,19,20,21,22] is raising attention, and pointing to the need for future research exploring possible underlying mechanisms, which could be responsible for the sex differences in the susceptibility to these diseases. It is important to ensure that the risk of high body iron stores is not increased as this may have detrimental effects on the brain and cause neurodegeneration and other neurological disorders [23,24]. The aim of this review is to provide an up-to-date discussion in iron metabolism, age-related changes, along with the sex differences in iron content in serum and brain, within the healthy aging population and in neurological disorders such as MS, PD, AD, and stroke
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