Center for Experimental Medicine, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
JAMA Neurol. 2013 Jan;70(1):20-4. doi: 10.1001/jamaneurol.2013.572.
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.
帕金森病是最常见的与衰老相关的神经退行性疾病之一。至少有 18 个遗传位点和 13 个与帕金森病相关的基因被确定。其中，由 F-box 仅蛋白 7 基因 (FBXO7) 突变引起的帕金森病，也称为帕金森-锥体束疾病 (PPD)。帕金森-锥体束疾病与典型帕金森病的主要区别在于发病年龄早和痉挛。在所有报道的 PPD 家族中，已经发现了四种突变，并提出了常染色体隐性遗传模式。FBXO7 蛋白是 Skp1-Cullin-F-box 型 E3 泛素连接酶的成员，在将蛋白质靶向泛素化中发挥重要作用。尽管 PPD 是一种相对罕见的帕金森病，但了解其遗传和病理机制可能会为帕金森病的发病机制以及不仅针对 PPD 而且针对其他帕金森病的治疗策略的发展提供新的见解。
