Nogo provides a molecular marker for diagnosis of amyotrophic lateral sclerosis.
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.
Dupuis
Luc
L
Laboratoire de Signalisations Moléculaires et Neurodégénérescence, EA 3433, Faculté de Médecine, Université Louis Pasteur, 11 rue Humann, 67085 Strasbourg Cedex, France.
Gonzalez de Aguilar
Jose-Luis
JL
di Scala
Franck
F
Rene
Frédérique
F
de Tapia
Marc
M
Pradat
Pierre-François
PF
Lacomblez
Lucette
L
Seihlan
Danielle
D
Prinjha
Rabinder
R
Walsh
Frank S
FS
Meininger
Vincent
V
Loeffler
Jean-Philippe
JP
D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005819:Genetic Markers / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D020125:Mutation, Missense / Q000235:genetics; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000235:genetics; D000070798:Nogo Proteins; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism
D005819:Genetic Markers; D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse