Proteasomal inhibition causes loss of nigral tyrosine hydroxylase neurons

被引：69

作者：

Schapira, Anthony H. V.

Cleeter, Michael W. J.

Muddle, John R.

Workman, Jane M.

Cooper, J. Mark

King, Rosalind H. M.

机构：

[1] Royal Free & Univ Coll, Sch Med, Univ Dept Clin Neurosci, London NW3 2PH, England

[2] UCL, Inst Neurol, London, England

来源：

ANNALS OF NEUROLOGY | 2006年 / 60卷 / 02期

关键词：

D O I：

10.1002/ana.20934

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Dysfunction of the ubiquitin-proteasomal system (UPS) has been implicated in the pathogenesis of Parkinson's disease. The systemic administration of UPS inhibitors has been reported to induce nigrostriatal cell death and model Parkinson's disease pathology in rodents. We administered a synthetic, specific UPS inhibitor (PSI) subcutaneously to rats and quantified substantia nigral tyrosine hydroxylase-positive dopaminergic neurons by stereology. PSI caused a 15% decrease in UPS activity at 2 weeks and a 42% reduction in substantia nigra pars compacta tyrosine hydroxylase-positive neurons at 8 weeks. Systemic inhibition of the UPS warrants further evaluation as a means to model Parkinson's disease.

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页码：253 / 255

页数：3

相关论文

共 15 条

[1] The proteasomal inhibition model of Parkinson's disease: "Boon or bust"? [J].

Beal, Flint ;

Lang, Anthony .

ANNALS OF NEUROLOGY, 2006, 60 (02) :158-161

[2] Proteasome inhibition and Parkinson's disease modeling [J].

Bove, Jordi ;

Zhou, Chun ;

Jackson-Lewis, Vernice ;

Taylor, Julie ;

Chu, Yaping ;

Rideout, Hardy J. ;

Wu, Du-Chu ;

Kordower, Jeffrey H. ;

Petrucelli, Leonard ;

Przedborski, Serge .

ANNALS OF NEUROLOGY, 2006, 60 (02) :260-264

[3] Lactacystin and clasto-lactacystin beta-lactone modify multiple proteasome beta-subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation [J].

Craiu, A ;

Gaczynska, M ;

Akopian, T ;

Gramm, CF ;

Fenteany, G ;

Goldberg, AL ;

Rock, KL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (20) :13437-13445

[4] Molecular pathways of neurodegeneration in Parkinson's disease [J].

Dawson, TM ;

Dawson, VL .

SCIENCE, 2003, 302 (5646) :819-822

[5] CHRONIC NICOTINE TREATMENT COUNTERACTS NIGRAL CELL LOSS INDUCED BY A PARTIAL MESODIENCEPHALIC HEMITRANSECTION - AN ANALYSIS OF THE TOTAL NUMBER AND MEAN VOLUME OF NEURONS AND GLIA IN SUBSTANTIA-NIGRA OF THE MALE-RAT [J].

JANSON, AM ;

MOLLER, A .

NEUROSCIENCE, 1993, 57 (04) :931-941

[6] Proteasome inhibitors: from research tools to drug candidates [J].

Kisselev, AF ;

Goldberg, AL .

CHEMISTRY & BIOLOGY, 2001, 8 (08) :739-758

[7] Failure of proteasome inhibitor administration to provide a model of Parkinson's disease in rats and monkeys [J].

Kordower, Jeffrey H. ;

Kanaan, Nicholas M. ;

Chu, Yaping ;

Babu, Rangasamy Suresh ;

Stansell, James, III ;

Terpstra, Brian T. ;

Sortwell, Caryl E. ;

Steece-Collier, Kathy ;

Collier, Timothy J. .

ANNALS OF NEUROLOGY, 2006, 60 (02) :264-268

[8] Lack of nigrostriatal pathology in a rat model of proteasome inhibition [J].

Manning-Bog, Amy B. ;

Reaney, Stephen H. ;

Chou, Vivian P. ;

Johnston, Louisa C. ;

McCormack, Alison L. ;

Johnston, Jennifer ;

Langston, J. William ;

Di Monte, Donato A. .

ANNALS OF NEUROLOGY, 2006, 60 (02) :256-260

[9] Proteasome inhibitor-induced model of Parkinson's disease [J].

McNaught, Kevin St. P. ;

Olanow, C. Warren .

ANNALS OF NEUROLOGY, 2006, 60 (02) :243-247

[10] Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease [J].

McNaught, KSP ;

Perl, DP ;

Brownell, AL ;

Olanow, CW .

ANNALS OF NEUROLOGY, 2004, 56 (01) :149-162