TY - JOUR
T1 - Iron dysregulation in movement disorders
AU - Dusek, Petr
AU - Jankovic, Joseph
AU - Le, Weidong
N1 - Funding Information:
This work was supported by the Czech Ministry of Health: IGA MZ ČR NT12282-5/2011 and by the Czech Ministry of Education: research project MŠM 0021620849. We also wish to acknowledge the support of the Baylor's Centers of Excellence by the National Parkinson Foundation and the Huntington Disease Society of America.
PY - 2012/4
Y1 - 2012/4
N2 - Iron is an essential element necessary for energy production, DNA and neurotransmitter synthesis, myelination and phospholipid metabolism. Neurodegeneration with brain iron accumulation (NBIA) involves several genetic disorders, two of which, aceruloplasminemia and neuroferritinopathy, are caused by mutations in genes directly involved in iron metabolic pathway, and others, such as pantothenate-kinase 2, phospholipase-A2 and fatty acid 2-hydroxylase associated neurodegeneration, are caused by mutations in genes coding for proteins involved in phospholipid metabolism. Phospholipids are major constituents of myelin and iron accumulation has been linked to myelin derangements. Another group of NBIAs is caused by mutations in lysosomal enzymes or transporters such as ATP13A2, mucolipin-1 and possibly also β-galactosidase and α-fucosidase. Increased cellular iron uptake in these diseases may be caused by impaired recycling of iron which normally involves lysosomes. Abnormal iron utilization by mitochondria, as has been proposed in Friedreich's ataxia, is another possible mechanism of iron accumulation. Other, more common degenerative movement disorders, such as Parkinson's disease, Huntington's disease, multiple system atrophy and progressive supranuclear palsy also exhibit increased brain iron content. Finally, brain iron deficiency has been implicated in restless legs syndrome. This review provides an update on recent findings related to genetics, pathogenic mechanisms, diagnosis, and treatment of movement disorders associated with dysregulation of brain iron. We also propose a new classification of NBIAs.
AB - Iron is an essential element necessary for energy production, DNA and neurotransmitter synthesis, myelination and phospholipid metabolism. Neurodegeneration with brain iron accumulation (NBIA) involves several genetic disorders, two of which, aceruloplasminemia and neuroferritinopathy, are caused by mutations in genes directly involved in iron metabolic pathway, and others, such as pantothenate-kinase 2, phospholipase-A2 and fatty acid 2-hydroxylase associated neurodegeneration, are caused by mutations in genes coding for proteins involved in phospholipid metabolism. Phospholipids are major constituents of myelin and iron accumulation has been linked to myelin derangements. Another group of NBIAs is caused by mutations in lysosomal enzymes or transporters such as ATP13A2, mucolipin-1 and possibly also β-galactosidase and α-fucosidase. Increased cellular iron uptake in these diseases may be caused by impaired recycling of iron which normally involves lysosomes. Abnormal iron utilization by mitochondria, as has been proposed in Friedreich's ataxia, is another possible mechanism of iron accumulation. Other, more common degenerative movement disorders, such as Parkinson's disease, Huntington's disease, multiple system atrophy and progressive supranuclear palsy also exhibit increased brain iron content. Finally, brain iron deficiency has been implicated in restless legs syndrome. This review provides an update on recent findings related to genetics, pathogenic mechanisms, diagnosis, and treatment of movement disorders associated with dysregulation of brain iron. We also propose a new classification of NBIAs.
KW - Chelating agents
KW - Dystonia
KW - Iron
KW - Neurodegeneration
KW - Parkinson's disease
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U2 - 10.1016/j.nbd.2011.12.054
DO - 10.1016/j.nbd.2011.12.054
M3 - Review article
C2 - 22266337
AN - SCOPUS:84858157347
SN - 0969-9961
VL - 46
SP - 1
EP - 18
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -