Neurodegenerative Disease
In healthy aging, selective accumulation of iron occurs in several brain regions and cell types, however, excessive accumulation of iron in specific brain regions occurs in many neurodegenerative diseases and is often associated with oxidative stress and cellular damage. Aging is a major risk factor for neurodegeneration, while age-related iron accumulation may be an important factor contributing to the neurodegenerative process.
Iron Metabolism in Human Brain
Iron enters the endothelium of the blood-brain barrier as a low-molecular-weight complex, either through transferrin receptor-1-mediated endocytosis of transferrin, or independently as non-transferrin-bound iron. The transferrin receptor is arranged in the brain lumen, binds circulating different transferrin, and facilitates iron uptake into cerebrovascular endothelial cells via receptor-mediated endocytosis.
Iron distribution in healthy brain tissue [1].
Iron Metabolism in Neurodegenerative Diseases
Protein aggregation of α-synuclein and hyperphosphorylated tau proteins in neurodegenerative diseases have been shown to be triggered in vitro by elevated concentrations of trivalent iron. Inclusion bodies containing damaged or aggregated proteins may lead to endoplasmic reticulum stress, a common feature of several neurodegenerative disorders.
| Disease Name | Iron Metabolism Abnormalities |
| Alzheimer's Disease | High levels of iron are present in insoluble amyloid plaques and neurogenic fiber tangles characteristic of Alzheimer's disease. Focal accumulation of iron may deprive other brain tissues of these essential metals, leading to abnormal neuronal function. |
| Parkinson Disease | Patients with Parkinson's disease have increased total nigrostriatal iron concentrations, and the high concentrations of iron detected in the substantia nigra may exceed the iron-buffering capacity of complexes such as neuromelanin and ferritin and may induce neurotoxicity. |
| Friedreich's Ataxia | Friedreich's ataxia (also known as FA or FRDA) is a genetic disorder that causes progressive damage to the nervous system. It can lead to muscle weakness, speech difficulties or heart disease. |
| Multiple Sclerosis | Elevated iron concentrations occur in specific brain regions in multiple sclerosis, most notably in deep gray matter structures, and increase in many deep gray matter structures as multiple sclerosis progresses. |
| Huntington's Disease | Alterations in brain iron metabolism with increased iron accumulation were identified in the striata of patients with Huntington's disease and in particular the basal ganglia. |
| Restless Legs Syndrome | Restless legs syndrome is characterized by reduced iron function. The reduced iron concentration in the substantia nigra of patients with restless legs syndrome correlates with the severity of the disease. |
Mitochondria Iron Metabolism Abnormalities in Neurodegenerative Diseases
In Friedreich's ataxia (FA), mutations in mitochondrial FXN lead to impaired Fe-S cluster biogenesis, which further leads to disruption of iron metabolism and an increase in mitochondrial iron content. In Huntington's disease (HD), the presence of mutant mHTT leads to increased sensitivity of NMDA receptors, and mHTT interacts with mitochondria, resulting in impaired mitochondrial membrane permeability.
Iron ions are involved in the development of neurodegenerative diseases by catalyzing the production of free radicals. Protheragen provide research services related to cerebral ischemia, iron metabolism disorders and neurodegenerative diseases, helping our clients to conduct in-depth research on the etiology of neurodegenerative diseases and provide new therapeutic ideas for the prevention and treatment of neurodegenerative diseases. If you are interested in the services we offer, please contact us for more information.
Reference
- Ward R J, et al. The role of iron in brain ageing and neurodegenerative disorders[J]. The Lancet Neurology, 2014, 13(10): 1045-1060.