Deep Proteomic Evaluation of Primary and Cell Line Motoneuron Disease Models Delineates

The fatal neurodegenerative disorders amyotrophic lat-eral sclerosis and spinal muscular atrophy are, respec-tively, the most common motoneuron disease and genetic cause of infant death. Various in vitromodel systems have been established to investigate motoneuron disease mechanisms, in particular immortalized cell lines and pri-mary neurons. Using quantitative mass-spectrometry-based proteomics, we compared the proteomes of pri-mary motoneurons to motoneuron-like cell lines NSC-34 and N2a, as well as to non-neuronal control cells, at a depth of 10,000 proteins. We used this resource to eval-uate the suitability of murine in vitro model systems for cell biological and biochemical analysis of motoneuron disease mechanisms. Individual protein and pathway analysis indicated substantial differences between mo