F-box only protein 7 gene in parkinsonian-pyramidal disease.

Center for Experimental Medicine, Third Xiangya Hospital, Central South University, Changsha, Hunan, China. hdeng008@yahoo.com

JAMA neurology 2013 Jan

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.