Nogo provides a molecular marker for diagnosis of amyotrophic lateral sclerosis

被引:138
作者
Dupuis, L
de Aguilar, JLG
di Scala, F
Rene, F
de Tapia, M
Pradat, PF
Lacomblez, L
Seihlan, D
Prinjha, R
Walsh, FS
Meininger, V
Loeffler, JP
机构
[1] Univ Strasbourg 1, Fac Med, Lab Signalisat Mol & Neurodegenerescence, F-67085 Strasbourg, France
[2] Hop La Pitie Salpetriere, Serv Neurol, F-75651 Paris 13, France
[3] Hop La Pitie Salpetriere, Serv Neuropathol, F-75651 Paris 13, France
[4] GlaxoSmithKline, Neurol CEDD, Neurodegenerat Dept, Harlow CM19 5AW, Essex, England
关键词
D O I
10.1006/nbdi.2002.0522
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by the selective degeneration of upper and lower motor neurons. The lack of a molecular diagnostic marker is of increasing concern in view of the therapeutic strategies in development. Using an unbiased subtractive suppressive hybridization screen we have identified a clone encoding the neurite outgrowth inhibitor Nogo and shown that its isoforms display a characteristic altered expression in ALS. This was first confirmed by analyzing Nogo isoform expression in a transgenic ALS model at early asymptomatic stages where we found increased levels of Nogo-A and decreased Nogo-C and importantly, not following experimentally induced denervation. Furthermore, we confirmed these changes in both post-mortem and biopsy samples from diagnosed ALS patients but not control patients. Thus, the alteration in Nogo expression pattern, common to sporadic and familial ALS, represents a potential diagnosis tool and points strongly to Nogo having a central role in disease. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:358 / 365
页数:8
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