Search results for "prion"

Pharmacological intervention in age-associated brain disorders by Flupirtine: Alzheimer’s and Prion diseases

1998

Alzheimer's disease, a major form of dementia in the elderly has become an increasingly important health problem in developed countries. In vitro studies on primary neurons demonstrate that Flupirtine (Katadolon) at a concentration of 1 microg/ml, significantly reduces the neurotoxic (apoptotic) effect displayed by A beta25-35, a segment of the amyloid beta-protein precursor the etiologic agent of Alzheimer's disease. Flupirtine, which has been in clinical use since 10 years ago, prevents the toxic effect of PrP, the presumed etiologic agent of the Creutzfeldt-Jakob disease as well as the excitatory amino acid glutamate on cortical neurons. Flupirtine displays a bimodal activity. Its strong…

Cellular Prion Protein Participates in Amyloid-β Transcytosis across the Blood—Brain Barrier

2012

The blood—brain barrier (BBB) facilitates amyloid-β (Aβ) exchange between the blood and the brain. Here, we found that the cellular prion protein (PrPc), a putative receptor implicated in mediating Aβ neurotoxicity in Alzheimer's disease (AD), participates in Aβ transcytosis across the BBB. Using an in vitro BBB model, [125I]-Aβ1–40 transcytosis was reduced by genetic knockout of PrPc or after addition of a competing PrPc-specific antibody. Furthermore, we provide evidence that PrPc is expressed in endothelial cells and, that monomeric Aβ1–40 binds to PrPc. These observations provide new mechanistic insights into the role of PrPc in AD.

Role of the cellular prion protein in oligodendrocyte precursor cell proliferation and differentiation in the developing and adult mouse CNS

2012

There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion protein (PrP c) to this process remains unclear. PrP c is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrP c influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrP c proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyt…

How copper ions and membrane environment influence the structure of the human and chicken tandem repeats domain?

2019

Abstract Prion proteins (PrPs) from different species have the enormous ability to anchor copper ions. The N-terminal domain of human prion protein (hPrP) contains four tandem repeats of the –PHGGGWGQ– octapeptide sequence. This octarepeat domain can bind up to four Cu2+ ions. Similarly to hPrP, chicken prion protein (chPrP) is able to interact with Cu2+ through the tandem hexapeptide -HNPGYP- region (residues 53–94). In this work, we focused on the human octapeptide repeat (human Octa4, hPrP60–91) (Ac-PHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQ-NH2) and chicken hexapeptide repeat (chicken Hexa4, chPrP54–77) (Ac-HNPGYPHNPGYPHNPGYPHNPGYP-NH2) prion protein fragments. Due to the fact that PrP is a membr…

Mode of action of Bacillus thuringiensis PS86Q3 strain in hymenopteran forest pests

2001

The mode of action of Cry toxins has been described principally in lepidopteran insects as a multistep process. In this work we describe the mode of action of a Cry toxin active in the common pine sawfly Diprion pini (Hymenoptera, Diprionidae), considered a major forest pest in Europe. Strain PS86Q3 contains a long bipyramidal crystal composed of five major proteins. The N-terminal sequence shows that the 155 kDa protein corresponds to Cry5B toxin and the other proteins belong to the Cry5A subgroup. PCR analysis indicates the presence of cry5Ac and cry5Ba genes, suggesting that Cry5A protein should be Cry5Ac. Activation of protoxins with trypsin or with midgut content from D. pini and Cepha…

Lenalidomide induced reversible parkinsonism, dystonia, and dementia in subclinical Creutzfeldt-Jakob disease

2018

Kinetics of expression of prion protein in uninfected and scrapie-infected N2a mouse neuroblastoma cells.

1993

The scrapie prion protein, PrPSc, is formed from its isoform, the cellular PrPc. There is evidence available indicating that PrPSc is necessary component of the infectious prion particle to cause a series of transmissible spongiform encephalopathies. We have used immunocytochemistry and RNA blotting techniques to investigate if infection with prions results in an increased PrP gene expression. For the experiments we used N2a cells which had been infected with prions (ScN2a cells). We demonstrated by confocal laser scanning microscopy that PrP-protein was present in the nucleus (predominantly in the nucleoli) of ScN2a cells. Analysis of the PrP-mRNA levels both in N2a- and in ScN2a cells usi…

Glycosylation deficiency at either one of the two glycan attachment sites of cellular prion protein preserves susceptibility to bovine spongiform enc…

2004

The conversion into abnormally folded prion protein (PrP) plays a key role in prion diseases. PrP(C) carries two N-linked glycan chains at amino acid residues 180 and 196 (mouse). Previous in vitro data indicated that the conversion process may not require glycosylation of PrP. However, it is conceivable that these glycans function as intermolecular binding sites during the de novo infection of cells on susceptible organisms and/or play a role for the interaction of both PrP isoforms. Such receptor-like properties could contribute to the formation of specific prion strains. However, in earlier studies, mutations at the glycosylation sites of PrP led to intracellular trafficking abnormalitie…

Prion protein gene frequencies in three Sicilian dairy sheep populations

2008

The objective of this paper was to investigate the prion protein (PrP) genotype and haplotype frequencies in three Sicilian dairy sheep populations. The three populations were: (1) 1096 Valle del Belice animals, (2) 1143 Comisana animals, and (3) 1771 individuals from 5 flocks with scrapie outbreaks, in which the animals were crossbreds derived from indigenous Sicilian dairy breeds. PrP genotypes are described for the three codons 136 (Alanine or Valine; A, V), 154 (Histidine or Arginine; H, R), and 171 (Glutamine, Arginine or Histidine; Q, R, H) which represent polymorphisms known to be linked with scrapie susceptibility. The Valle del Belice haplotype frequencies were 32.3% ARR, 6.5% AHQ,…

PrP Gene Polymorphism in Medieval Remains of Sicilian Sheep

2015

Encephalopathy in sheep was at first described in Ireland in 1732 and was called scrapie. Ancient DNA in archaeogenetics represents an effective method to evaluate the ancestral pedigree of living animals and track evolutionary changes occurred between the past and the present day. Since several point mutations are today widely described in modern scrapie, no data about both sequence and frequency are still available for the prion protein (PrP) gene in ancient breeds. In order to evaluate whether the haplotypes distribution in ancient sheep differed from those of the modern population we evaluated polymorphism at four well know codons of the Prp Open Reading Frame. In the present work, we c…