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.