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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)
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)
  • D R Brown
  • 2000
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)
There is now strong evidence to show that the presence of the cellular prion protein (PrP(C)) mediates amyloid-β (Aβ) neurotoxicity in Alzheimer's disease (AD). Here, we probe the molecular details of the interaction between PrP(C) and Aβ and discover that substoichiometric amounts of PrP(C), as little as 1/20, relative to Aβ will strongly inhibit amyloid(More)
In obesity-related hypertension, activation of the renin-angiotensin system (RAS) has been reported despite marked fluid volume expansion. Adipose tissue expresses components of the RAS and is markedly expanded in obesity. This study evaluated changes in components of the adipose and systemic RAS in diet-induced obese hypertensive rats. RAS was quantified(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)
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)
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)
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)