Luc Dupuis,
Jose-Luis Gonzalez de Aguilar,
Franck di Scala,
Frédérique Rene,
Marc de Tapia,
Pierre-François Pradat,
Lucette Lacomblez, Danielle Seihlan,
Rabinder Prinjha,
Frank S Walsh,
Vincent Meininger,
Jean-Philippe Loeffler
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ABSTRACT: 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.
Neurobiology of Disease 09/2002; 10(3):358-65. · 5.40 Impact Factor
