Functional Genetics of Spastin

Mutations in the human spastin gene (SPG4) cause the most prevalent form of autosomal dominant hereditary spastic paraplegia (HSP), a neurodegenerative disorder characterized by progressive weakness and spasticity of the lower limbs. Human spastin is ubiquitously expressed and encodes a member of the AAA (ATPases associated with various cellular activities) protein family which is characterized by a conserved domain with ATPase activity. In a previous study, using polyclonal antibodies against the N-terminal spastin sequence, we have shown that the native protein is localized in both the perinuclear cytoplasm an…