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The cellular function of the prion protein (PrPc), a cell surface glycoprotein expressed in neurones and astrocytes, has not been elucidated. Cell culture experiments reveal that cerebellar cells lacking PrPc are more sensitive to oxidative stress and undergo cell death more readily than wild-type cells. This effect is reversible by treatment with vitamin(More)
In prion disease neurodegeneration requires deposition of the abnormal isoform of the prion protein (PrP(Sc)) within nervous tissue. In vitro PrP(Sc) has neurotoxicity that can be mimicked by peptides based on part of its sequence. In this investigation the region of the protein required for maximal neurotoxicity was precisely determined. The optimal(More)
Prion diseases are characterized by the conversion of the normal cellular prion protein (PrP(C)) into a pathogenic isoform (PrP(Sc)). PrP(C) binds copper, has superoxide dismutase (SOD)-like activity in vitro, and its expression aids in the cellular response to oxidative stress. However, the interplay between PrPs (PrP(C), PrP(Sc) and possibly other(More)
Although minor abnormalities have been reported in prion protein (PrP) knock-out (Prnp-/-) mice, the normal physiological function of PrP, the causative agent implicated in transmissible spongiform encephalopathies (TSE), remains unresolved. Since there are increasing correlations between oxidative stress and amyloidoses, we decided to investigate whether(More)
The prion protein (PrPc) is a normal cellular protein expressed by neurones and astrocytes. An altered isoform, PrPSc is thought to transmit spongiform encephalopathies. Here we show that microglia also express PrPc. Sensitivity of microglia to activation is enhanced by increased expression of PrPc. Bacterial endotoxin increases superoxide production and(More)
A considerable body of evidence suggests that UV light disrupts ligand binding in vitro. In vivo, UV light effects have been reported to disrupt simple behaviors such as spontaneous locomotor activity. However, there are no reports of UV light blocking a more complex drug-altered behavior. We now report that: (1) cocaine dose-relatedly reversed planarians'(More)
FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian beta-tubulin that polymerizes and assembles into a ring to initiate cell division. We have created a class of small synthetic antibacterials, exemplified by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent and selective in vitro bactericidal(More)
Opioids and cannabinoids have profound inhibitory actions on intestinal motility which are mediated in part by their cognate receptors in the enteric nervous system. In the present study, we examined the expression of immunoreactivity for delta- and kappa-opioid receptors, CB(1)-cannabinoid receptors and type 1 vanilloid receptors by immunocytochemistry and(More)
Interactions of sympathetic nerve activity (SNA) with blood pressure (BP) and heart rate (HR) were assessed in conscious rats while they rested quietly in a cloth sock (n = 7), roamed freely in their home cage (n = 6), and then after anesthesia with pentobarbital (30 mg/kg; n = 7). The power and coherence spectra below 3 Hz were calculated from data(More)
Alpha-synuclein is a natively unfolded protein that aggregates and forms inclusions that are associated with a range of diseases that include Parkinson's Disease and Dementia with Lewy Bodies. The mechanism behind the formation of these inclusions and their possible role in disease remains unclear. Alpha-synuclein has also been shown to bind metals(More)