Brain Iron Metabolism and Neurodegenerative Disorders

Abstract

Iron, an essential element for central nervous system (CNS) function, has frequently been found to accumulate in brain regions that undergo degeneration in neurological diseases such as Alzheimer disease, Parkinson disease, Friedreich ataxia and other disorders. However, the precise role of iron in the cause of many neurodegenerative diseases is unclear. To assist in understanding the potential importance of iron in CNS disease, this review summarizes the present knowledge in the areas of CNS iron metabolism, homeostasis and disregulation of iron balance caused by mutations in genes encoding proteins involved in iron transport, storage and metabolism. This review encompasses neurodegenerative disorders associated with both iron overload and deficiency to highlight areas where iron misregulation is likely to be important in the pathophysiology of several human brain diseases.

Determination of brain iron content in patients with Parkinson’s disease using magnetic susceptibility imaging

“…Iron accumulation [10][11][12][13] in the brain occurs in PD, and measuring the amount of nonheme iron in the body may not only lead to a better understanding of the disease progression, but also help to predict the outcome in relation to patients' motor symptom.…”

Different Iron-Deposition Patterns of Multiple System Atrophy with Predominant Parkinsonism and Idiopathetic Parkinson Diseases Demonstrated by Phase-Corrected Susceptibility-Weighted Imaging

“…Many methods have been used to detect iron accumulation in neurodegenerative diseases. [10][11][12][13][14][15][16][17][18][19][20][21] However, these methods may be insufficient for detecting subtle changes in iron components associated with disease progression and may not be sensitive enough to detect and discriminate IPD from MSA-P. 22,23 SWI is a new technique that exploits the magnetic properties of iron content of tissues by using magnitude and phase images with a 3D fully velocitycompensated gradient-echo sequence. Compared with a standard T2* sequence, thin sections with 3D SWI are used to avoid background field T2* signal intensity loss and magnetic field variations.…”

The Potential Relationship between the Incidence of Neurodegenerative Disease and Trace Mineral Composition in the Drinking Water of Rural Residents of Ontario

“…Damage to the ubiquitin-proteasome system can also occur, resulting in aggregation and accumulation of defective proteins due to lack of protein clearance [11] [22]. Free radical formation occurs at a greater rate in certain areas of the brain, making these regions more susceptible to damage ensued by the processes that take place, like the Fenton reaction [9] [23]. Metal exposure can cause genetic damage, as well as influence reactivation or silencing of gene expression [11] [24].…”

“…Ions of trace and heavy metals such as iron, manganese, aluminum, mercury, lead, copper, chromium and cadmium have been linked to the initiation of numerous neurodegenerative disorders [1] [7] [8]. Iron especially has received attention with regards to Parkinson's, Alzheimer's and multiple sclerosis; researchers have localized the ion's accumulation to regions of the brain that have been recognized to undergo deterioration in these disease states [9] [10]. Peripheral and central nervous system regions which are notably affected include the spinal motor neurons for ALS, the cortex, basal forebrain, brain stem, and hippocampus in Alzhemier's, the cortex, substantia nigra, and locus ceruleus for Parkinson's, and the cortex, basal ganglia and striatum for Huntington's disease [11].…”

“…Abnormalities at the genetic level have been proven to be largely influential in disorders of the brain like Parkinson's, Alzheimer's and Multiple Sclerosis [9] [10]. However, this does not discount the important role that heavy metals can play during the manifestation of these disorders; studies have pinpointed various malfunctioning metal ion carriers that appear to be involved.…”