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The neurite outgrowth inhibitor Nogo‐A promotes denervation in an amyotrophic lateral sclerosis model
Author(s) -
Jokic Natasa,
Gonzalez de Aguilar JoseLuis,
Dimou Leda,
Lin Shuo,
Fergani Anissa,
Ruegg Markus A,
Schwab Martin E,
Dupuis Luc,
Loeffler JeanPhilippe
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400826
Subject(s) - amyotrophic lateral sclerosis , denervation , axon , neurite , motor neuron , neuroscience , regeneration (biology) , biology , neuromuscular junction , microbiology and biotechnology , anatomy , medicine , disease , pathology , spinal cord , biochemistry , in vitro
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.