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

2006; Springer Nature; Volume: 7; Issue: 11 Linguagem: Inglês

10.1038/sj.embor.7400826

1469-3178

Nataša Ivančić Jokić, José‐Luis González de Aguilar, Leda Dimou, Shuo Lin, Anissa Fergani, Markus A. Rüegg, Martin E. Schwab, Luc Dupuis, Jean‐Philippe Loeffler,

Neurogenetic and Muscular Disorders Research

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.