Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease

被引：1006
作者：
Auluck, PK
Chan, HYE
Trojanowski, JQ
Lee, VMY
Bonini, NM [1 ]
机构：
[1] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA
[3] Univ Penn, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA
[4] Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA
[5] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[6] Univ Penn, Sch Med, Philadelphia, PA 19104 USA
来源：
SCIENCE | 2002年 / 295卷 / 5556期
关键词：
D O I：
10.1126/science.1067389
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Parkinson's disease is a movement disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Dopaminergic neuronal loss also occurs in Drosophila melanogaster upon directed expression of alpha-synuclein, a protein implicated in the pathogenesis of Parkinson's disease and a major component of proteinaceous Lewy bodies. We report that directed expression of the molecular chaperone, Hsp70 prevented dopaminergic neuronal loss associated with alpha-synuclein in Drosophila and that interference with endogenous chaperone activity accelerated alpha-synuclein toxicity. Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinson's disease progression.
引用
收藏
页码：865 / 868
页数：4
相关论文
共 22 条
[1]  
Baba M, 1998, AM J PATHOL, V152, P879
[2]  
BRAND AH, 1993, DEVELOPMENT, V118, P401
[3]   The Hsp70 and Hsp60 chaperone machines [J].
Bukau, B ;
Horwich, AL .
CELL, 1998, 92 (03) :351-366
[4]   ROLE OF THE CHAPERONE PROTEIN HSP104 IN PROPAGATION OF THE YEAST PRION-LIKE FACTOR [PSI(+)] [J].
CHERNOFF, YO ;
LINDQUIST, SL ;
ONO, B ;
INGEVECHTOMOV, SG ;
LIEBMAN, SW .
SCIENCE, 1995, 268 (5212) :880-884
[5]   Tissue-specific expression of dominant negative mutant Drosophila HSC70 causes developmental defects and lethality [J].
Elefant, F ;
Palter, KB .
MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (07) :2101-2117
[6]   A Drosophila model of Parkinson's disease [J].
Feany, MB ;
Bender, WW .
NATURE, 2000, 404 (6776) :394-398
[7]   Identification of genes that modify ataxin-1-induced neurodegeneration [J].
Fernandez-Funez, P ;
Nino-Rosales, ML ;
de Gouyon, B ;
She, WC ;
Luchak, JM ;
Martinez, P ;
Turiegano, E ;
Benito, J ;
Capovilla, M ;
Skinner, PJ ;
McCall, A ;
Canal, I ;
Orr, HT ;
Zoghbi, HY ;
Botas, J .
NATURE, 2000, 408 (6808) :101-106
[8]  
Giasson BI, 2000, J NEUROSCI RES, V59, P528, DOI 10.1002/(SICI)1097-4547(20000215)59:4<528::AID-JNR8>3.0.CO
[9]  
2-0
[10]   Hsp104, Hsp70, and Hsp40: A novel chaperone system that rescues previously aggregated proteins [J].
Glover, JR ;
Lindquist, S .
CELL, 1998, 94 (01) :73-82
123