The neurite outgrowth inhibitor Nogo-A promotes denervation in an amyotrophic lateral sclerosis model

• Published in: EMBO reports 2006-11, Vol.7 (11), p.1162-1167
• Main Authors: Jokic, Natasa, Gonzalez de Aguilar, Jose-Luis, Dimou, Leda, Lin, Shuo, Fergani, Anissa, Ruegg, Markus A, Schwab, Martin E, Dupuis, Luc, Loeffler, Jean-Philippe
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - chemically induced; Amyotrophic Lateral Sclerosis - therapy; Animals; Disease Models, Animal; G86R mouse; Gene expression; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular biology; Muscle Denervation; Muscles; Muscles - innervation; Muscles - metabolism; Muscular system; Myelin Proteins - genetics; Myelin Proteins - metabolism; Myelin Proteins - physiology; neuromuscular junction; Neuromuscular Junction - physiopathology; Nogo Proteins; Nogo-A; Rodents; Scientific Report; skeletal muscle; Superoxide Dismutase - genetics; Superoxide Dismutase-1; Transfection
• ISSN: 1469-221X; 1469-3178; 1469-221X
• DOI: 10.1038/sj.embor.7400826

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.