Prednisone reduces muscle degeneration in dystrophin-deficient Caenorhabditis elegans

被引:66
作者
Gaud, A
Simon, JM
Witzel, T
Carre-Pierrat, M
Wermuth, CG
Ségalat, L
机构
[1] Univ Lyon 1, CNRS, UMR 5534, CGMC, F-69622 Villeurbanne, France
[2] Prestwick Chem Inc, F-67400 Illkirch Graffenstaden, France
关键词
dystrophin; Duchenne muscular dystrophy; nematode;
D O I
10.1016/j.nmd.2004.02.011
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Duchenne muscular dystrophy is a degenerative muscular disease caused by mutations in the dystrophin gene. There is no curative treatment against Duchenne muscular dystrophy. In several countries, the steroid prednisone (or analogs) is prescribed as a palliative treatment. In the model animal Caenorhabditis elegans, mutations of the dys-1 dystrophin-like gene lead to a muscular degenerative phenotype when they are associated with a mild MyoD mutation. This cheap and fast-growing model of dystrophinopathy may be used to screen for molecules able to slow muscle degeneration. In a blind screen of approximately 100 compounds covering a wide spectrum of targets, we found that prednisone is beneficial to the C elegans dystrophin-deficient muscles. Prednisone reduces by 40% the number of degenerating cells in this animal. This result is a proof-of-principle for the use of C. elegans as a tool in the search for molecules active against the effects of dystrophin-deficiency. Moreover, since C. elegans is not susceptible to inflammation, this suggests that prednisone exerts a direct effect on muscle survival. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:365 / 370
页数:6
相关论文
共 19 条
[1]   THE STRUCTURAL AND FUNCTIONAL DIVERSITY OF DYSTROPHIN [J].
AHN, AH ;
KUNKEL, LM .
NATURE GENETICS, 1993, 3 (04) :283-291
[2]   Mutations in the Caenorhabditis elegans dystrophin-like gene dys-1 lead to hyperactivity and suggest a link with cholinergic transmission [J].
Bessou, C ;
Giugia, JB ;
Franks, CJ ;
Holden-Dye, L ;
Ségalat, L .
NEUROGENETICS, 1998, 2 (01) :61-72
[3]  
BRENNER S, 1974, GENETICS, V77, P71
[4]   Transcriptional activation of the utrophin promoter B by a constitutively active Ets-transcription factor [J].
Briguet, A ;
Bleckmann, D ;
Bettan, M ;
Mermod, N ;
Meier, T .
NEUROMUSCULAR DISORDERS, 2003, 13 (02) :143-150
[5]  
Dubowitz V, 2000, J ROY COLL PHYS LOND, V34, P464
[6]   Genetic suppression of phenotypes arising from mutations in dystrophin-related genes in Caenorhabditis elegans [J].
Gieseler, K ;
Grisoni, K ;
Ségalat, L .
CURRENT BIOLOGY, 2000, 10 (18) :1092-1097
[7]   Overexpression of dystrobrevin delays locomotion defects and muscle degeneration in a dystrophin-deficient Caenorhabditis elegans [J].
Gieseler, K ;
Grisoni, K ;
Mariol, MC ;
Ségalat, L .
NEUROMUSCULAR DISORDERS, 2002, 12 (04) :371-377
[8]   Genetic evidence for a dystrophin-glycoprotein complex (DGC) in Caenorhabditis elegans [J].
Grisoni, K ;
Martin, E ;
Gieseler, K ;
Mariol, MC ;
Ségalat, L .
GENE, 2002, 294 (1-2) :77-86
[9]   COMPLETE CLONING OF THE DUCHENNE MUSCULAR-DYSTROPHY (DMD) CDNA AND PRELIMINARY GENOMIC ORGANIZATION OF THE DMD GENE IN NORMAL AND AFFECTED INDIVIDUALS [J].
KOENIG, M ;
HOFFMAN, EP ;
BERTELSON, CJ ;
MONACO, AP ;
FEENER, C ;
KUNKEL, LM .
CELL, 1987, 50 (03) :509-517
[10]   Muscular degeneration in the absence of dystrophin is a calcium-dependent process [J].
Mariol, MC ;
Ségalat, L .
CURRENT BIOLOGY, 2001, 11 (21) :1691-1694