title: Prions in variably protease-sensitive prionopathy: an update.
abstract: Human prion diseases, including sporadic, familial, and acquired forms such as Creutzfeldt-Jakob disease (CJD), are caused by prions in which an abnormal prion protein (PrPSc) derived from its normal cellular isoform (PrPC) is the only known component. The recently-identified variably protease-sensitive prionopathy (VPSPr) is characterized not only by an atypical clinical phenotype and neuropathology but also by the deposition in the brain of a peculiar PrPSc. Like other forms of human prion disease, the pathogenesis of VPSPr also currently remains unclear. However, the findings of the peculiar features of prions from VPSPr and of the possible association of VPSPr with a known genetic prion disease linked with a valine to isoleucine mutation at residue 180 of PrP reported recently, may be of great importance in enhancing our understanding of not only this atypical human prion disease in particular, but also other prion diseases in general. In this review, we highlight the physicochemical and biological properties of prions from VPSPr and discuss the pathogenesis of VPSPr including the origin and formation of the peculiar prions.
authors.affiliation: Department of Pathology Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. wenquan.zou@case.edu.
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Zou
authors.affiliation: Department of Pathology Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. pxg13@case.edu.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
authors.affiliation: Department of Pathology Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. xiangzhu.xiao@case.edu.
authors.forename: Xiangzhu
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pathology Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. jue.yuan@case.edu.
authors.forename: Jue
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Central Veterinary Institute of Wageningen UR, Lelystad 8200 AB, the Netherlands. jan.langeveld@wur.nl.
authors.forename: Jan
authors.initials: J
authors.lastname: Langeveld
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299 00161, Rome, Italy. laura.pirisinu@guest.iss.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Pirisinu