The neurite outgrowth inhibitor Nogo-A promotes denervation in an amyotrophic lateral sclerosis model.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss and muscle wasting. In muscles of ALS patients, Nogo-A-a protein known to inhibit axon regeneration-is ectopically expressed at levels that correlate with the severity of the clinical symptoms. We now show that the genetic ablation of Nogo-A extends survival and reduces muscle denervation in a mouse model of ALS. In turn, overexpression of Nogo-A in wild-type muscle fibres leads to shrinkage of the postsynapse and retraction of the presynaptic motor ending. This suggests that the expression of Nogo-A occurring early in ALS skeletal muscle could cause repulsion and destabilization of the motor nerve terminals, and subsequent dying back of the axons and motor neurons.
Jokic
Natasa
N
Inserm, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, 11 rue Humann, F-67085 Strasbourg, France.
Gonzalez de Aguilar
Jose-Luis
JL
Dimou
Leda
L
Lin
Shuo
S
Fergani
Anissa
A
Ruegg
Markus A
MA
Schwab
Martin E
ME
Dupuis
Luc
L
Loeffler
Jean-Philippe
JP
D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009121:Muscle Denervation; D009132:Muscles / Q000294:innervation / Q000378:metabolism*; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009469:Neuromuscular Junction / Q000503:physiopathology; D000070798:Nogo Proteins; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014162:Transfection
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1