VCP expression decrease as a biomarker of preclinical and early clinical stages of Parkinson’s disease
Valosin-containing human protein (VCP) or p97 performs enzyme functions associated with the maintenance of protein homeostasis and control of protein quality. Disruption of its normal functioning might be associated with the development of Parkinson’s disease (PD). Tissues of mice with toxininduced presymptomatic and early symptomatic stages of PD, as well as 52 treated and untreated patients with newly diagnosed PD and nine patients with a “predicted” form of PD, were investigated. Signifcant changes in Vcp gene expression were observed in almost all studied mouse tissues. A signifcant decrease in VCP expression specifc for PD was also detected at both the late preclinical and the early clinical stages of PD in untreated patients. Thus, a decrease in VCP expression is important for changes in the function of the nervous system at early stages of PD. Analysis of changes in VCP expression in all patients with PD and in Vcp in the peripheral blood of mice used as models of PD revealed signifcant decreases in expression specifc for PD. These data suggest that a decrease in the relative levels of VCP mRNA might serve as a biomarker for the development of pathology at the early clinical and preclinical stages of human PD.