Most cited article - PubMed ID 34441299
Molecular Pathology of ALS: What We Currently Know and What Important Information Is Still Missing
Trace elements and vitamins, collectively known as micronutrients, are essential for basic metabolic reactions in the human body. Their deficiency or, on the contrary, an increased amount can lead to serious disorders. Research in recent years has shown that long-term abnormal levels of micronutrients may be involved in the etiopathogenesis of some neurological diseases. Acute and chronic alterations in micronutrient levels may cause other serious complications in neurological diseases. Our aim was to summarize the knowledge about micronutrients in relation to selected neurological diseases and comment on their importance and the possibilities of therapeutic intervention in clinical practice.
- Keywords
- Huntington’s disease, Parkinson’s disease, autoimmune disorders, epilepsy, micronutrients, multiple sclerosis, neurodegenerative disorders, neuropathy, stroke,
- MeSH
- Humans MeSH
- Micronutrients MeSH
- Nervous System Diseases * MeSH
- Trace Elements * MeSH
- Vitamin A MeSH
- Vitamins MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Micronutrients MeSH
- Trace Elements * MeSH
- Vitamin A MeSH
- Vitamins MeSH
Disruption of cerebral iron regulation appears to have a role in aging and in the pathogenesis of various neurodegenerative disorders. Possible unfavorable impacts of iron accumulation include reactive oxygen species generation, induction of ferroptosis, and acceleration of inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow the examination of macroscopic patterns of brain iron deposits in vivo, while modern analytical methods ex vivo enable the determination of metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes the whole brain, cellular, and subcellular patterns of iron accumulation in neurodegenerative diseases of genetic and sporadic origin. We also provide an update on mechanisms, biomarkers, and effects of brain iron accumulation in these disorders, focusing on recent publications. In Parkinson's disease, Friedreich's disease, and several disorders within the neurodegeneration with brain iron accumulation group, there is a focal siderosis, typically in regions with the most pronounced neuropathological changes. The second group of disorders including multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis shows iron accumulation in the globus pallidus, caudate, and putamen, and in specific cortical regions. Yet, other disorders such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest with diffuse iron accumulation in the deep gray matter in a pattern comparable to or even more extensive than that observed during normal aging. On the microscopic level, brain iron deposits are present mostly in dystrophic microglia variably accompanied by iron-laden macrophages and in astrocytes, implicating a role of inflammatory changes and blood-brain barrier disturbance in iron accumulation. Options and potential benefits of iron reducing strategies in neurodegeneration are discussed. Future research investigating whether genetic predispositions play a role in brain Fe accumulation is necessary. If confirmed, the prevention of further brain Fe uptake in individuals at risk may be key for preventing neurodegenerative disorders.
- Keywords
- MRI, NBIA, chelation, ferroptosis, iron accumulation, neurodegeneration, siderosis,
- MeSH
- Humans MeSH
- Brain pathology MeSH
- Neuroaxonal Dystrophies * pathology MeSH
- Neurodegenerative Diseases * pathology MeSH
- Iron Metabolism Disorders * pathology MeSH
- Iron pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Iron MeSH