Iron metabolism in the CNS: implications for neurodegenerative diseases
Abstract
Abnormal accumulation of brain iron has been detected in various neurodegenerative diseases, but the contribution of iron overload to pathology remains unclear. In a group of distinctive brain iron overload diseases known as 'neurodegeneration with brain iron accumulation' (NBIA) diseases, nine disease genes have been identified. Brain iron accumulation is observed in the globus pallidus and other brain regions in NBIA diseases, which are often associated with severe dystonia and gait abnormalities. Only two of these diseases, aceruloplasminaemia and neuroferritinopathy, are directly caused by abnormalities in iron metabolism, mainly in astrocytes and neurons, respectively. Understanding the early molecular pathophysiology of these diseases should aid insights into the role of iron and the design of specific therapeutic approaches.
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Iron-mediated generation of ROS and injury to mitochondria are likely mechanisms of NBIA.
“Although iron-mediated generation of ROS and injury to mitochondria are likely mechanisms [196, 204]”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [196]
In other rare genetic diseases of the neurodegeneration with brain iron accumulation group, mutations disrupt proteins with cellular functions different from iron metabolism, and the mechanisms that result in brain iron overload are undefined.
“In other rare genetic diseases of this group, such as pantothenate kinase-associated neurodegeneration, phospholipase A2G6-associated neurodegeneration, and Kufor-Rakeb disease, mutations disrupt proteins with cellular functions different from iron metabolism, and the mechanisms that result in brain iron overload are undefined.169–173”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [170]
In iron overloaded areas of the brain in aceruloplasminaemia, up to a ten-times increase was recorded in neurons and microglia, but widespread brain iron deposition can occur.
“In these iron overloaded areas of the brain, up to a ten-times increase was recorded in neurons and microglia, but widespread brain iron deposition can occur.170,175”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [170]
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Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease
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“Thismay be the reasonwhy no efficient specific treatment has been yet developed, the therapy relying only on symptomatic alleviation [2–4].”
BackgroundAbsence of iron-responsive element-binding protein 2 causes a novel neurodegenerative syndrome.
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Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis
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- Authors
- Rouault, T. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Rouault, Tracey A.
- ORCID
- Rouault, Tracey A.
- Venue
- Nature Reviews Neuroscience
- Published
- 2013-07-03
- Volume
- 14
- Issue
- 8
- Pages
- 551-564
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2025048194
- Cited by
- 496
- References
- 143
- Citations by year
- 2026: 38 · 2025: 46 · 2024: 35 · 2023: 33 · 2022: 49 · 2021: 47 · 2020: 25 · 2019: 41 · 2018: 33 · 2017: 43 · 2016: 29 · 2015: 39 · 2014: 32 · 2013: 6
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- brain iron accumulation, iron metabolism, neurodegeneration with brain iron accumulation, iron overload, neuroferritinopathy, globus pallidus, dystonia, gait disturbance, astrocytes, neurons, molecular pathophysiology, treatment options
- MeSH terms
- Animals, Central Nervous System, Humans, Iron, Iron Metabolism Disorders, Neurodegenerative Diseases
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