Chronic ferritin expression within murine dopaminergic midbrain neurons results in a progressive age-related neurodegeneration

被引：35

作者：

Kaur, Deepinder

Rajagopalan, Subrarnanian

Chinta, Shankar

Kumar, Jyothi

Di Monte, Donato

Cherny, Robert A.

Andersen, Julie K.

机构：

[1] Buck Inst Res Aging, Novato, CA 94945 USA

[2] Parkinsons Inst, Sunnyvale, CA 94089 USA

[3] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia

[4] Mental Hlth Res Inst, Parkville, Vic 3052, Australia

来源：

BRAIN RESEARCH | 2007年 / 1140卷

关键词：

iron chelation; ferritin; aging; dopamine; neurodegeneration; Parkinson's disease;

D O I：

10.1016/j.brainres.2006.03.006

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Ferritin elevation has been reported by some laboratories to occur within the substantia nigra (SN), the area of the brain affected in Parkinson's disease (PD), but whether such an increase could be causatively involved in neurodegeneration associated with the disorder is unknown. Here, we report that chronic ferritin elevation in midbrain dop amine-containing neurons results in a progressive age-related neurodegeneration of these cells. This provides strong evidence that chronic ferritin overload could be directly involved in age-related neurodegeneration such as occurs in Parkinson's and other related diseases. (c) 2006 Elsevier B.V. All rights reserved.

引用

收藏

页码：188 / 194

页数：7

相关论文

共 26 条

[1] Brain ferritin iron as a risk factor for age at onset in neurodegenerative diseases [J].

Bartzokis, G ;

Tishler, TA ;

Shin, IS ;

Lu, PH ;

Cummings, JL .

REDOX-ACTIVE METALS IN NEUROLOGICAL DISORDERS, 2004, 1012 :224-236

[2]

CHEN JC, 1993, AM J NEURORADIOL, V14, P275

[3]

CONNOR JR, 1995, J NEUROCHEM, V65, P717

[4] Neuroferritinopathy: A window on the role of iron in neurodegeneration [J].

Crompton, DE ;

Chinnery, PF ;

Fey, C ;

Curtis, ARJ ;

Morris, CM ;

Kierstan, J ;

Burt, A ;

Young, F ;

Coulthard, A ;

Curtis, A ;

Ince, PG ;

Bates, D ;

Jackson, MJ ;

Burn, J .

BLOOD CELLS MOLECULES AND DISEASES, 2002, 29 (03) :522-531

[5] Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease [J].

Curtis, ARJ ;

Fey, C ;

Morris, CM ;

Bindoff, LA ;

Ince, PG ;

Chinnery, PF ;

Coulthard, A ;

Jackson, MJ ;

Jackson, AP ;

McHale, DP ;

Hay, D ;

Barker, WA ;

Markham, AF ;

Bates, D ;

Curtis, A ;

Burn, J .

NATURE GENETICS, 2001, 28 (04) :350-354

[6] ALTERATIONS IN THE LEVELS OF IRON, FERRITIN AND OTHER TRACE-METALS IN PARKINSONS-DISEASE AND OTHER NEURODEGENERATIVE DISEASES AFFECTING THE BASAL GANGLIA [J].

DEXTER, DT ;

CARAYON, A ;

JAVOYAGID, F ;

AGID, Y ;

WELLS, FR ;

DANIEL, SE ;

LEES, AJ ;

JENNER, P ;

MARSDEN, CD .

BRAIN, 1991, 114 :1953-1975

[7]

Double KL, 1998, J NEUROCHEM, V70, P2492

[8] Lack of up-regulation of ferritin is associated with sustained iron regulatory protein-1 binding activity in the substantia nigra of patients with Parkinson's disease [J].

Faucheux, BA ;

Martin, ME ;

Beaumont, C ;

Hunot, S ;

Hauw, JJ ;

Agid, Y ;

Hirsch, EC .

JOURNAL OF NEUROCHEMISTRY, 2002, 83 (02) :320-330

[9] Altered body iron distribution and rmicrocytosis in mice deficient in iron regulatory protein 2 (IRP2) [J].

Galy, B ;

Ferring, D ;

Minana, B ;

Bell, O ;

Janser, HG ;

Muckenthaler, M ;

Schümann, K ;

Hentze, MW .

BLOOD, 2005, 106 (07) :2580-2589

[10] Iron in the basal ganglia in Parkinson's disease -: An in vitro study using extended X-ray absorption fine structure and cryo-electron microscopy [J].

Griffiths, PD ;

Dobson, BR ;

Jones, GR ;

Clarke, DT .

BRAIN, 1999, 122 :667-673