Iron Metabolism of the Skeletal Muscle and Neurodegeneration

Abstract

Recent studies clearly indicate that the endocrine function of the skeletal muscle is essential for a long and healthy life. Regular exercise, which has been shown to stimulate the release of myokines, lowers the risk of many diseases, including Alzheimer’s and Parkinson’s disease, emphasizing the role of skeletal muscle in proper functioning of other tissues. In addition, exercise increases insulin sensitivity, which may also impact iron metabolism. Even though the role of iron in neurodegeneration is well established, the exact mechanisms of iron toxicity are not known. Interestingly, exercise has been shown to modulate iron metabolism, mainly by reducing body iron stores. Insulin signaling and iron metabolism are interconnected, as high tissue iron stores are associated with insulin resistance, and conversely, impaired insulin signaling may lead to iron accumulation in an affected tissue. Excess iron accumulation in tissue triggers iron-dependent oxidative stress. Further, iron overload in the skeletal muscle not only negatively affects muscle contractility but also might impact its endocrine function, thus possibly affecting the clinical outcome of diseases, including neurodegenerative diseases. In this review, we discuss possible mechanisms of iron dependent oxidative stress in skeletal muscle, its impact on muscle mass and endocrine function, as well as on neurodegeneration processes.

Exercise Training and Vitamin C Supplementation Affects Ferritin mRNA in Leukocytes without Affecting Prooxidative/Antioxidative Balance in Elderly Women

“…Furthermore, FOXO3a and CAT have apoptosis-regulation properties [28,29]. Recently it has been shown that FOXO3a controls the expression of ferritin and catalase mRNA [30,31], thus the next goal of this study was to determine the effect of training and supplementation on the expression of these genes. Unfortunately, no significant changes were observed for FOXO3a and CAT mRNA.…”

Effect of Ischemic Preconditioning on Marathon-Induced Changes in Serum Exerkine Levels and Inflammation

“…In animal models, TNF infusion induces decrement in the left ventricular performance (Pagani et al, 1992). In the skeletal muscle, proinflammatory cytokines induce several deleterious changes, including an increase in oxidative stress activation atrophy, delay in muscle recovery, and many others (Halon-Golabek et al, 2019). In addition, high oxygen demand by the skeletal muscle leads to augmented generation of reactive oxygen species (ROS), which stimulate inflammation (Radak et al, 2013).…”

Gene co-expression network analysis in human spinal cord highlights mechanisms underlying amyotrophic lateral sclerosis susceptibility

“…We identified 13 total co- Intriguingly, PTPN23 and NCOA4, hubs in the SC.M4 and SC.M2 modules respectively, are involved in the autophagy of ferritin 40,41 , which may link iron metabolism and neurodegeneration via these genes' involvement in iron metabolism and ferroptosis 42 . Ferritin has been found to be elevated in serum and cerebrospinal fluid (CSF) from ALS patients [43][44][45] , and recent work implicates iron metabolism in muscle health, suggesting serum ferritin as a potential biomarker in ALS 46 . Based on this, we hypothesize that disruptions in autophagy of ferritin are involved at early stages of ALS pathophysiology.…”