scholarly journals Atypical Prion Protein Conformation in Familial Prion Disease with PRNP P105T Mutation

2010 ◽  
Vol 21 (2) ◽  
pp. 209-214 ◽  
Author(s):  
Magdalini Polymenidou ◽  
Stefan Prokop ◽  
Hans H. Jung ◽  
Ekkehard Hewer ◽  
David Peretz ◽  
...  
Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 193
Author(s):  
Min-Ju Jeong ◽  
Yong-Chan Kim ◽  
Byung-Hoon Jeong

Pathogenic prion protein (PrPSc), converted from normal prion protein (PrPC), causes prion disease. Although prion disease has been reported in several mammalian species, chickens are known to show strong resistance to prion diseases. In addition to chickens, the domestic duck occupies a large proportion in the poultry industry and may be regarded as a potential resistant host against prion disease. However, the DNA sequence of the prion protein gene (PRNP) has not been reported in domestic ducks. Here, we performed amplicon sequencing targeting the duck PRNP gene with the genomic DNA of Pekin ducks. In addition, we aligned the PrP sequence of the Pekin duck with that of various species using ClustalW2 and carried out phylogenetic analysis using Molecular Evolutionary Genetics Analysis X (MEGA X). We also constructed the structural modeling of the tertiary and secondary structures in avian PrP using SWISS-MODEL. Last, we investigated the aggregation propensity on Pekin duck PrP using AMYCO. We first reported the DNA sequence of the PRNP gene in Pekin ducks and found that the PrP sequence of Pekin ducks is more similar to that of geese than to that of chickens and mallards (wild ducks). Interestingly, Pekin duck PrP showed a high proportion of β-sheets compared to that of chicken PrP, and a high aggregation propensity compared to that of avian PrPs. However, Pekin duck PrP with substitutions of chicken-specific amino acids showed reduced aggregation propensities. To the best of our knowledge, this is the first report on the genetic characteristics of the PRNP sequence in Pekin ducks.


Author(s):  
Hiroyuki Honda ◽  
Kosuke Matsuzono ◽  
Kota Satoh ◽  
Masayoshi Fujisawa ◽  
Satoshi O. Suzuki ◽  
...  

2004 ◽  
Vol 98 (1) ◽  
pp. 133-143 ◽  
Author(s):  
David R Brown ◽  
Valeria Guantieri ◽  
Giulia Grasso ◽  
Giuseppe Impellizzeri ◽  
Giuseppe Pappalardo ◽  
...  

1998 ◽  
Vol 95 (21) ◽  
pp. 12580-12585 ◽  
Author(s):  
P. Tremblay ◽  
Z. Meiner ◽  
M. Galou ◽  
C. Heinrich ◽  
C. Petromilli ◽  
...  

2017 ◽  
Vol 474 (19) ◽  
pp. 3253-3267 ◽  
Author(s):  
Alana M. Thackray ◽  
Alzbeta Cardova ◽  
Hanna Wolf ◽  
Lydia Pradl ◽  
Ina Vorberg ◽  
...  

Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt–Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrPSc, an abnormal isomer of the normal host protein PrPC, in the brain of affected individuals. PrPSc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila. We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila. Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host.


2021 ◽  
Vol 134 (17) ◽  
Author(s):  
Caihong Zhu ◽  
Adriano Aguzzi

ABSTRACT Prion diseases are neurodegenerative disorders caused by conformational conversion of the cellular prion protein (PrPC) into scrapie prion protein (PrPSc). As the main component of prion, PrPSc acts as an infectious template that recruits and converts normal cellular PrPC into its pathogenic, misfolded isoform. Intriguingly, the phenomenon of prionoid, or prion-like, spread has also been observed in many other disease-associated proteins, such as amyloid β (Aβ), tau and α-synuclein. This Cell Science at a Glance and the accompanying poster highlight recently described physiological roles of prion protein and the advanced understanding of pathogenesis of prion disease they have afforded. Importantly, prion protein may also be involved in the pathogenesis of other neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therapeutic studies of prion disease have also exploited novel strategies to combat these devastating diseases. Future studies on prion protein and prion disease will deepen our understanding of the pathogenesis of a broad spectrum of neurodegenerative conditions.


Neuroreport ◽  
2007 ◽  
Vol 18 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Jennifer K. Griffin ◽  
Linda A. Terry ◽  
Roy Jackman ◽  
Masoud Yousefi ◽  
Neil R. Cashman

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