Parkinson disease is one of the most common
neurodegenerative diseases associated with aging. At least 18 genetic loci and 13 disease-related genes for
parkinsonism have been identified. Among them, PARK15 -associated
parkinsonism, also referred to as parkinsonian-pyramidal disease (
PPD), was found to be caused by mutations in the F-box only
protein 7 gene (FBXO7). Parkinsonian-pyramidal disease differs from typical
Parkinson disease chiefly by juvenile onset and the presence of spasticity. Four mutations have been identified and a pattern of autosomal recessive inheritance has been proposed in all reported
PPD families. The FBXO7
protein is a member of the Skp1-Cullin-F-box-type E3
ubiquitin ligases, which play important roles in targeting
proteins for ubiquitination. Although
PPD is a relatively rare parkinsonian disorder, understanding its genetic and pathological mechanisms may lead to new insights into the pathogenesis of
Parkinson disease and development of therapeutic strategies not only for
PPD but also for other
parkinsonian disorders.