It is well defined that subpopulations of motoneurons have different vulnerability to the pathology causing amyotrophic lateral sclerosis (ALS). In the spinal cord, the fast fatigable motoneurons have been shown to be the first to degenerate, followed by fatigue-resistant and slow motoneurons. In contrast motoneurons located in the Onuf’s and oculomotor nuclei appear to be resistant to disease. With a focus on research mainly done on mice overexpressing the mutated human superoxide dismutase (SOD1) protein, we review recent studies exploring the mechanisms that underlie the selective vulnerability of the various motoneuron subtypes. By comparing differences in gene expression between these populations, it has been possible to identify factors, which critically determine the survival of motoneurons and the neuromuscular function in the pathologic context of ALS. Furthermore, we discuss the contribution of non-cell autonomous processes, involving glial cells and the skeletal muscle, in the neurodegenerative process. Exploring the cause of neurodegeneration from the angle of the selective neuronal vulnerability has recently led to the identification of novel targets, which open opportunities for therapeutic intervention against ALS.
Part of the book: Update on Amyotrophic Lateral Sclerosis