Nitric oxide (NO) production is implicated in muscle contraction, growth and atrophy, and in the onset of neuropathy. However, many aspects of the mechanism of action of NO are not yet clarified, mainly regarding its role in muscle wasting. Notably, whether NO production-associated neuromuscular atrophy depends on tyrosine nitration or S-nitrosothiols (SNOs) formation is still a matter of debate. Here, we aim at assessing this issue by characterizing the neuromuscular phenotype of S-nitrosoglutathione reductase-null (GSNOR-KO) mice that maintain the capability to produce NO, but are unable to reduce SNOs. We demonstrate that, GSNOR-KO mice suffer from muscle wasting without any involvement of tyrosine nitrationassociated damage. Functional analysis of muscle strength provide the first evidence that young GSNOR-KO mice show clear signs of muscle atrophy and neuropathic behavior, condition that is associated with muscle wasting in elderly people. Mitochondria appear fragmented and depolarized in GSNOR-KO myofibers and myotubes, and are reverted by N-acetylcysteine treatment. Nevertheless, although atrogene transcription is induced, and bulk-autophagy activated, no removal of damaged mitochondria is observed. These events, alongside basal increase of apoptotic markers, contribute to persistence of a neuropathic and myopathic state. In this phD thesis we provide evidence that GSNOR physiologically underwent silencing during aging. It is plausible to speculate, therefore, that nitrosative stress occurring upon GSNOR deficiency, could compromise mitochondrial function, resembling, in such a way, aging-like conditions. Our study provides the first evidence that that the genetic ablation of GSNOR results in a clinically relevant neuromuscular phenotype resembling neuropathic pain-associated muscle atrophy. Our results indicate that GSNOR and nitrosative stress could represent elective targets for denitrosylating agent-based therapies.