The role of iron in brain ageing and neurodegenerative disorders

被引:1432
作者
Ward, Roberta [1 ,2 ]
Zucca, Fabio A. [3 ]
Duyn, Jeff H. [4 ]
Crichton, Robert R. [2 ]
Zecca, Luigi [3 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Ctr Neuroinflammat & Neurodegenerat, Dept Med, London, England
[2] Catholic Univ Louvain, Fac Sci, Louvain La Neuve, Belgium
[3] Natl Res Council Italy, Inst Biomed Technol, Milan, Italy
[4] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA
关键词
RESTLESS LEGS SYNDROME; AMYLOID-PRECURSOR-PROTEIN; HEME OXYGENASE-1 EXPRESSION; MILD COGNITIVE IMPAIRMENT; CENTRAL-NERVOUS-SYSTEM; OXIDATIVE DNA-DAMAGE; X-RAY-MICROANALYSIS; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; ALZHEIMERS-DISEASE;
D O I
10.1016/S1474-4422(14)70117-6
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
In the CNS, iron in several proteins is involved in many important processes such as oxygen transportation, oxidative phosphorylation, myelin production, and the synthesis and metabolism of neurotransmitters. Abnormal iron homoeostasis can induce cellular damage through hydroxyl radical production, which can cause the oxidation and modification of lipids, proteins, carbohydrates, and DNA. During ageing, different iron complexes accumulate in brain regions associated with motor and cognitive impairment. In various neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, changes in iron homoeostasis result in altered cellular iron distribution and accumulation. MRI can often identify these changes, thus providing a potential diagnostic biomarker of neurodegenerative diseases. An important avenue to reduce iron accumulation is the use of iron chelators that are able to cross the blood-brain bather, penetrate cells, and reduce excessive iron accumulation, thereby affording neuroprotection.
引用
收藏
页码:1045 / 1060
页数:16
相关论文
共 226 条
[1]   Astrocyte-endothelial interactions at the blood-brain barrier [J].
Abbott, NJ ;
Rönnbäck, L ;
Hansson, E .
NATURE REVIEWS NEUROSCIENCE, 2006, 7 (01) :41-53
[2]   The role of iron in restless legs syndrome [J].
Allen, Richard P. ;
Earley, Christopher J. .
MOVEMENT DISORDERS, 2007, 22 :S440-S448
[3]   MRI measurement of brain iron in patients with restless legs syndrome [J].
Allen, RP ;
Barker, PB ;
Wehrl, F ;
Song, HK ;
Earley, CJ .
NEUROLOGY, 2001, 56 (02) :263-265
[4]   Iron Toxicity in Diseases of Aging: Alzheimer's Disease, Parkinson's Disease and Atherosclerosis [J].
Altamura, Sandro ;
Muckenthaler, Martina U. .
JOURNAL OF ALZHEIMERS DISEASE, 2009, 16 (04) :879-895
[5]   Forging a field: the golden age of iron biology [J].
Andrews, Nancy C. .
BLOOD, 2008, 112 (02) :219-230
[6]   Iron homeostasis [J].
Andrews, Nancy C. ;
Schmidt, Paul J. .
ANNUAL REVIEW OF PHYSIOLOGY, 2007, 69 :69-85
[7]   High field magnetic resonance microscopy of the human hippocampus in Alzheimer's disease: Quantitative imaging and correlation with iron [J].
Antharam, Vijay ;
Collingwood, Joanna F. ;
Bullivant, John-Paul ;
Davidson, Mark R. ;
Chandra, Saurav ;
Mikhaylova, Albina ;
Finnegan, Mary E. ;
Batich, Christopher ;
Forder, John R. ;
Dobson, Jon .
NEUROIMAGE, 2012, 59 (02) :1249-1260
[8]   Age-related Iron Deposition in the Basal Ganglia: Quantitative Analysis in Healthy Subjects [J].
Aquino, Domenico ;
Bizzi, Alberto ;
Grisoli, Marina ;
Garavaglia, Barbara ;
Bruzzone, Maria Grazia ;
Nardocci, Nardo ;
Savoiardo, Mario ;
Chiapparini, Luisa .
RADIOLOGY, 2009, 252 (01) :165-172
[9]   Ceruloplasmin dysfunction and therapeutic potential for Parkinson disease [J].
Ayton, Scott ;
Lei, Peng ;
Duce, James A. ;
Wong, Bruce X. W. ;
Sedjahtera, Amelia ;
Adlard, Paul A. ;
Bush, Ashley I. ;
Finkelstein, David I. .
ANNALS OF NEUROLOGY, 2013, 73 (04) :554-559
[10]   Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla [J].
Bagnato, Francesca ;
Hametner, Simon ;
Yao, Bing ;
van Gelderen, Peter ;
Merkle, Hellmut ;
Cantor, Fredric K. ;
Lassmann, Hans ;
Duyn, Jeff H. .
BRAIN, 2011, 134 :3599-3612