Cerebral Iron Deposition in Neurodegeneration
Abstract
:1. Introduction
2. Brain Iron, Neuroinflammation, and Cognitive Decline in Aging
Condition | Whole Body Level | Brain Level | ||
---|---|---|---|---|
Macroscopic | Cellular | Subcellular | ||
Aging | ↑ serum ferritin [53] | ↑ Fe in red nucleus, putamen, substantia nigra, dentate nucleus, globus pallidus, caudate nucleus, subthalamic nucleus, cortex [7] | Fe remains stable in oligodendroglia; Fe accumulates in astrocytes and dystrophic microglia in cortex and deep gray matter [12] | Fe bound to ferritin in cytoplasm of microglia and astrocytes and to neuromelanin in neurons [12,28] |
AceruloplasMinemia | ↑ Fe in liver, pancreas, retina ↑ serum ferritin, ↓ transferrin saturation [54,55] | ↑ Fe in putamen, caudate, lateral, habenular, and pulvinar thalamic nuclei, red nucleus, dentate nucleus, inner cortical layers, hippocampus, mammillary bodies, superior and inferior colliculi [56,57] | ↑ Fe in astrocytes, neurons [58,59,60] | Fe stored in ferritin/ hemosiderin in lysosomal dense bodies and cytoplasmic inclusions [61,62] |
Hereditary Ferritinopathy | ↑ Fe in liver, kidney, skin, muscle ↓ serum ferritin [63,64,65] | ↑ Fe in globus pallidus, substantia nigra, dentate nucleus, putamen, thalamus, caudate, deep cortical layers [66,67,68] | ↑ Fe in nuclei and cytoplasm of microglia, oligodendroglia, neurons, and also extracellularly [64,69] | Fe stored in inclusion bodies consisting of abnormal ferritin aggregates [69,70] |
Pantothenate Kinase-Associated Neurodegeneration | - | ↑ Fe in globus pallidus, substantia nigra [71,72,73,74] | ↑ Fe in astrocytes, neurons, perivascular macrophages, iron dust in neuropil [75,76] | Fe stored in cytoplasmic inclusions co-localized with ferritin [75] |
Mitochondrial Membrane Protein-Associated Neurodegeneration | - | ↑ Fe in globus pallidus, substantia nigra, putamen, caudate [77,78] | ↑ Fe in perivascular macrophages, astrocytes, neurons [79,80] | n.a. |
Phospholipase A2-Associated Neurodegeneration | - | ↑ Fe in globus pallidus, substantia nigra, dentate nucleus [81,82,83] | ↑ Fe perivascularly in extracellular deposits and in macrophages [82,84,85] | n.a. |
Beta-Propeller Protein-Associated Neurodegeneration | ↑ serum Tfr/logFerrit ratio [86] | ↑ Fe in substantia nigra, cerebral peduncles, globus pallidus [87] | ↑ Fe in excessive macrophages [88,89] | n.a. |
Friedreich Ataxia | Fe-positive granules in cardiomyocytes ↓ serum Fe [90,91,92,93] | ↑ Fe in dentate nucleus, red nucleus [94,95] | Fe switched from oligodendroglia to microglia in dentate nucleus [96,97,98] | Fe presumably primarily accumulated in mitochondria [99,100] |
Wilson Disease | ↑ Fe in liver ↑ serum Fe, ferritin, hepcidin, soluble transferrin receptor [101,102,103] | ↑ Fe in globus pallidus, putamen, caudate, thalamus, substantia nigra, red nucleus, subthalamic nucleus [104,105] | ↑ Fe in excessive macrophages, astrocytes [106] | n.a. |
Parkinson Disease | ↓ Fe in serum/plasma [107] | ↑ Fe in substantia nigra [108,109] | ↑ Fe in neurons and adjacent neuropil, microglia, perivascularly in extracellular deposits [110,111,112] | Fe bound to neuromelanin in dopaminergic neurons [112,113] |
Alzheimer Disease | ↓ Fe in serum/plasma [114,115,116] | ↑ Fe in (mostly temporal) cortex, globus pallidus, caudate, putamen [117,118,119,120,121,122] | ↑ Fe in amyloid plaques, microglia, along myelinated fibers [117,123,124,125] | Fe bound to amyloid partially composed of magnetite nanoparticles [126,127] |
Amyotrophic Lateral Sclerosis | ↑ ferritin, ↓ transferrin in serum [128] ↑ Fe in liver, kidneys [129] ↑ Fe in spinal cord [130,131] | ↑ Fe in motor cortex, caudate, subthalamic nucleus, globus pallidus, substantia nigra, red nucleus [132,133,134] | ↑ Fe in spinal cord neuron nuclei [135] ↑ Fe in microglia in motor cortex [136] | n.a. |
Multiple Sclerosis | - | ↑ Fe in globus pallidus, putamen, caudate ↓ Fe in normal appearing white matter and thalamus [137,138,139,140,141] | ↑ Fe in macrophages, activated microglia in the rim of lesions; in reactive astrocytes in the inactive centers of lesions; in oligodendroglia, astrocytes, and microglia in the deep gray matter [137,142,143,144,145] | Fe in active lesions stored in ferritin, hemosiderin, and magnetite [144] |
3. Neurodegenerations with Brain Iron Accumulation (NBIA) Group
4. Other Genetic Disorders with Brain Iron Deposits
5. Iron Accumulation and Pathology in Sporadic Neurodegenerative Disorders
6. Demyelinating Disorders and Neuroinflammation
7. Iron Chelation and Other Means to Decrease Cerebral Iron
8. Summary and Future Perspectives
9. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Dusek, P.; Hofer, T.; Alexander, J.; Roos, P.M.; Aaseth, J.O. Cerebral Iron Deposition in Neurodegeneration. Biomolecules 2022, 12, 714. https://doi.org/10.3390/biom12050714
Dusek P, Hofer T, Alexander J, Roos PM, Aaseth JO. Cerebral Iron Deposition in Neurodegeneration. Biomolecules. 2022; 12(5):714. https://doi.org/10.3390/biom12050714
Chicago/Turabian StyleDusek, Petr, Tim Hofer, Jan Alexander, Per M. Roos, and Jan O. Aaseth. 2022. "Cerebral Iron Deposition in Neurodegeneration" Biomolecules 12, no. 5: 714. https://doi.org/10.3390/biom12050714