Pathogenesis of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) in its most severe form (type 1) is a lethal neurodegenerative disease in children. It represents the most frequent genetic cause of death in this patient group and has a prevalence of 1: 5 000 live births. Aa yet there are no options for therapy. SMA is caused by a mutation or, respectively, deletion of the survival motoneuron 1 gene (Smn1) and proceeds through degeneration of motor neurons in the spinal cord. The SMN protein presumably has various functions: it serves as a platform for the formation of pre-mRNA splicing complexes - this splicing process takes place in the cell nucleus. Furthermore, SMN also plays a role in the axons of nerve cells. Preliminary work in our group has demonstrated that SMN regulates the growth of neurites and that in SMA there is a dysregulation of the actin cytoskeleton. The biochemical signalling pathway responsible for this dysregulation has been identified. It involves the rho-kinase (ROCK) signalling pathway - an important switch for various neuronal, actin-dependent processes. The ROCK molecule is thus also a suitable target molecule for pharmacological interventions.