Background information
Paraplegin is a 795 amino acid metalloprotease that is a member of the AAA protein family. Localized to the mitochrondrial membrane and expressed throughout the body, Paraplegin is a multi-pass membrane protein that is thought to be involved in signal transduction and chaperone-like activities in the mitochrondria. Defects in the gene encoding Paraplegin are the cause of spastic paraplegia type 7 (SPG7), a form of autosomal recessive hereditary spastic paraplegia (AR-HSP). HSPs are degenerative spinal cord disorders that are characterized by muscle spasms, stiffness in the legs and, in some cases, incontinence. Recent studies suggest that SPG7 may be a mitochondrial-based disease, as mutations in the Paraplegin gene lead to ragged-red fibers, oxidase-negative fibers and intense succinate dehydrogenase-stained areas of the mitochrondria. These mitochondrial dysfunctions lead to axonal degeneration and impaired axonal transport, thus causing the neurodegeneration seen in HSPs.
