Nogo provides a molecular marker for diagnosis of amyotrophic lateral sclerosis |
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Authors: | Dupuis Luc Gonzalez de Aguilar Jose-Luis di Scala Franck Rene Frédérique de Tapia Marc Pradat Pierre-François Lacomblez Lucette Seihlan Danielle Prinjha Rabinder Walsh Frank S Meininger Vincent Loeffler Jean-Philippe |
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Institution: | Laboratoire de Signalisations Moléculaires et Neurodégénérescence, EA 3433, Faculté de Médecine, Université Louis Pasteur, 11 rue Humann, 67085 Strasbourg Cedex, France. |
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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. |
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