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Chronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice. [ABSTRACT FROM AUTHOR]

Previous studies have suggested strong antifibrotic activity of curcumol in the liver; the underlying mechanisms of which, however, remain largely unknown. Aiming to investigate the role of curcumol in regulating early and advanced liver fibrosis, we designed a rat model with advanced liver fibrosis and cell model with an initial fibrotic stage. Model rats induced by CCl4 and alcohol presented advanced liver fibrosis with complete fibrous septa. The administration of curcumol (25 mg/kg or 50 mg/kg) resulted in reversal of liver fibrosis. Leptin-administrated liver sinusoidal endothelial cells presented defenestration and basement membrane components deposition, including laminin (LN) and type IV collagen (Col IV), the characteristics of capillarization by scanning electron microscopy and immunofluorescence assays. After treatment with curcumol (12.5, 25, or 50 mg/L), defenestration was restored and the levels of LN and Col IV were decreased, consistent with the rat model. Quantitative polymerase chain reaction and Western blot results revealed that increased levels of urokinase plasminogen activator (uPA)/ uPA receptor (uPAR) were observed both in vivo and in vitro, curcumol significantly reduced uPA/uPAR at both the mRNA and protein levels. Reduction of uPA/uPAR may be synergistic with matrix metallopeptidase 13 to reverse liver fibrogenesis. In conclusion, curcumol protects liver from phenotypic changes in the early and advanced fibrogenesis, possibly through uPA/uPAR pathway. [ABSTRACT FROM AUTHOR]

Although structurally and biochemically similar to the cellular prion (PrPC), doppel (Dpl) is unique in its biological functions. There are no reports about any neurodegenerative diseases induced by Dpl. However the artificial expression of Dpl in the PrP-deficient mouse brain causes ataxia with Purkinje cell death. Abundant Dpl proteins have been found in testis and depletion of the Dpl gene (Prnd) causes male infertility. Therefore, we hypothesize different regulations of Prnd in the nerve and male productive systems. In this study, by electrophoretic mobility shift assays we have determined that two different sets of transcription factors are involved in regulation of the Prnd promoter in mouse neuronal N2a and GC-1 spermatogenic (spg) cells, i.e., upstream stimulatory factors (USF) in both cells, Brn-3 and Sp1 in GC-1 spg cells, and Sp3 in N2a cells, leading to the expression of Dpl in GC-1 spg but not in N2a cells. We have further defined that, in N2a cells, Dpl induces oxidative stress and apoptosis, which stimulate ataxia-telangiectasia mutated (ATM)-modulating bindings of transcription factors, p53 and p21, to Prnp promoter, resulting the PrPC elevation for counteraction of the Dpl cytotoxicity; in contrast, in GC-1 spg cells, phosphorylation of p21 and N-terminal truncated PrP may play roles in the control of Dpl-induced apoptosis, which may benefit the physiological function of Dpl in the male reproduction system. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegenerative disease characterized by the production of β-amyloid proteins and hyperphosphorylation of tau protein. Inflammation and apoptotic severity were highly correlated with earlier age at onset of Alzheimer's disease and were also associated with cognitive decline. This study aims to examine whether the traditional Chinese medicine ginsennoside Rd could prevent cognitive deficit and take neuroprotective effects in β-amyloid peptide 1-40-induced rat model of Alzheimer's disease. To produce Alzheimer's disease animal model, aggregated β-amyloid peptide 1-40 injected into hippocampus bilaterally. Ginsennoside Rd protected their cognitive impairment and improved their memory function by daily intraperitoneal injection for 30 days consecutively. In addition, ginsennoside Rd alleviated the inflammation induced by β-amyloid peptide 1-40. Furthermore, ginsennoside Rd played a role in the down-regulation of caspase-3 proteins and reduced the apoptosis that normally followed β-amyloid peptide 1-40 injection. The results of this study showed that the pretreatment of ginsennoside Rd had neuroprotective effects in β-amyloid peptide 1-40-induced AD model rat. [ABSTRACT FROM AUTHOR]

Presents research which shows that the amino-terminal domain of prion protein exhibits five to six sites that bind copper (Cu(II)) presented as a glycine chelate. The binding that occurs at neutral Ph; How the findings indicate that prion protein can exist in a copper-metalloprotein form in vivo; Research method; Results.