Database : MEDLINE
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[PMID]: 29510738
[Au] Autor:Sacchi P; Rasero R; Ru G; Aiassa E; Colussi S; Ingravalle F; Peletto S; Perrotta MG; Sartore S; Soglia D; Acutis P
[Ad] Address:Department of Veterinary Science, Torino University, Turin, Italy.
[Ti] Title:Predicting the impact of selection for scrapie resistance on PRNP genotype frequencies in goats.
[So] Source:Vet Res;49(1):26, 2018 Mar 06.
[Is] ISSN:1297-9716
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The European Union has implemented breeding programmes to increase scrapie resistance in sheep. A similar approach can be applied also in goats since the K222 allele provides a level of resistance equivalent to that of ARR in sheep. The European Food Safety Authority stated that breeding for resistance could be offered as an option for Member States to control classical scrapie in goats. We assessed the impact of different breeding strategies on PRNP genotype frequencies using a mathematical model that describes in detail the evolution of K222 in two goat breeds, Chamois Coloured and Saanen. Different patterns of age structure and replacement rate were modelled as factors affecting response to selection. Breeding for scrapie resistance can be implemented in goats, even though the initial K222 frequencies in these breeds are not particularly favourable and the rate at which the resistant animals increase, both breeding and slaughtered for meat production, is slow. If the goal is not to achieve the fixation of resistance allele, it is advisable to carry out selection only until a desired frequency of K222-carriers has been attained. Nucleus selection vs. selection on the overall populations is less expensive but takes longer to reach the desired output. The programme performed on the two goat breeds serves as a model of the response the selection could have in other breeds that show different initial frequencies and population structure. In this respect, the model has a general applicability.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1186/s13567-018-0518-x

  2 / 7330 MEDLINE  
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[PMID]: 29468946
[Au] Autor:Haley NJ; Richt JA; Davenport KA; Henderson DM; Hoover EA; Manca M; Caughey B; Marthaler D; Bartz J; Gilch S
[Ad] Address:a Department of Microbiology and Immunology , Midwestern University , Glendale , AZ , USA.
[Ti] Title:Design, implementation, and interpretation of amplification studies for prion detection.
[So] Source:Prion;:1-10, 2018 Mar 09.
[Is] ISSN:1933-690X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Amplification assays for transmissible spongiform encephalopathies have been in development for close to 15 years, with critical implications for the postmortem and antemortem diagnosis of human and animal prion diseases. Little has been published regarding the structured development, implementation and interpretation of experiments making use of protein misfolding cyclic amplification (PMCA) and real time quaking-induced conversion (RT-QuIC), and our goal with this Perspectives manuscript is to offer a framework which might allow for more efficient expansion of pilot studies into diagnostic trials in both human and animal subjects. This framework is made up of approaches common to diagnostic medicine, including a thorough understanding of analytical and diagnostic sensitivity and specificity, an a priori development of amplification strategy, and an effective experimental design. It is our hope that a structured framework for prion amplification assays will benefit not only experiments seeking to sensitively detect naturally-occurring cases of prion diseases and describe the pathogenesis of TSEs, but ultimately assist with future endeavors seeking to use these methods more broadly for other protein misfolding disorders, including Alzheimer's and Parkinson's disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1080/19336896.2018.1443000

  3 / 7330 MEDLINE  
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[PMID]: 29330304
[Au] Autor:Pritzkow S; Morales R; Lyon A; Concha-Marambio L; Urayama A; Soto C
[Ad] Address:From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas 77030 and.
[Ti] Title:Efficient prion disease transmission through common environmental materials.
[So] Source:J Biol Chem;293(9):3363-3373, 2018 Mar 02.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Prion diseases are a group of fatal neurodegenerative diseases associated with a protein-based infectious agent, termed prion. Compelling evidence suggests that natural transmission of prion diseases is mediated by environmental contamination with infectious prions. We hypothesized that several natural and man-made materials, commonly found in the environments of wild and captive animals, can bind prions and may act as vectors for disease transmission. To test our hypothesis, we exposed surfaces composed of various common environmental materials ( wood, rocks, plastic, glass, cement, stainless steel, aluminum, and brass) to hamster-adapted 263K scrapie prions and studied their attachment and retention of infectivity and Our results indicated that these surfaces, with the sole exception of brass, efficiently bind, retain, and release prions. Prion replication was studied using the protein misfolding cyclic amplification technology, and infectivity of surface-bound prions was analyzed by intracerebrally challenging hamsters with contaminated implants. Our results revealed that virtually all prion-contaminated materials transmitted the disease at high rates. To investigate a more natural form of exposure to environmental contamination, we simply housed animals with large contaminated spheres made of the different materials under study. Strikingly, most of the hamsters developed classical clinical signs of prion disease and typical disease-associated brain changes. Our findings suggest that prion contamination of surfaces commonly present in the environment can be a source of disease transmission, thus expanding our understanding of the mechanisms for prion spreading in nature.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1074/jbc.M117.810747

  4 / 7330 MEDLINE  
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[PMID]: 28470584
[Au] Autor:Jang B; Jeon YC; Shin HY; Lee YJ; Kim H; Kondo Y; Ishigami A; Kim YS; Choi EK
[Ad] Address:Ilsong Institute of Life Science, Hallym University, 15 Gwanpyeong-ro 170beon-gil, Anyang, Gyeonggi-do, 14066, Republic of Korea.
[Ti] Title:Myelin Basic Protein Citrullination, a Hallmark of Central Nervous System Demyelination, Assessed by Novel Monoclonal Antibodies in Prion Diseases.
[So] Source:Mol Neurobiol;55(4):3172-3184, 2018 Apr.
[Is] ISSN:1559-1182
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Myelin basic protein (MBP) citrullination by peptidylarginine deiminase (PAD) enzymes leads to incomplete protein-lipid bilayer interactions and vulnerability to proteolytic enzymes, resulting in disorganization of the myelin sheath in the central nervous system. Therefore, citrullinated MBP (citMBP) has been suggested as a hallmark of demyelination, but how citMBP is implicated in prion diseases remains unknown. For the first time, we developed mouse monoclonal anti-citMBP IgG1 (clones 1B8, 1H1, and 3C6) and IgM (clone 3G5) antibodies that recognize human citMBP at its R25, R122, and R130 residues and at its C-terminal region (or the corresponding sites in mouse MBP), respectively. Using a biochemical, immunohistochemical, and immunogold-silver staining for electron microscopy techniques, we found that MBP residue R23 (corresponding to human R25) was specifically citrullinated, was stained as intense punctae in the corpus callosum, the striatum, and the cerebellar white matter, and was predominantly localized in disorganized myelin in the brains of scrapie-infected mice. In the brains of Creutzfeldt-Jakob disease (CJD) patients, MBP residues R25, R122, and R130 were markedly citrullinated and were stained as fibrils and punctae. In particular, white matter regions, such as the midbrain and the medulla, exhibited high levels of citMBP compared to other regions. However, the high levels of citMBP were not correlated with PAD2 expression. The clone 3G5 recognized significantly increased expression of the 18.5 kDa and/or 21.5 kDa variants of MBP in prion disease. Our findings suggest that significantly increased levels of citMBP may reflect demyelinating neuropathology, and that these newly developed antibodies may be useful for identifying demyelination.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1705
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1007/s12035-017-0560-0

  5 / 7330 MEDLINE  
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[PMID]: 28455699
[Au] Autor:Iaccarino L; Moresco RM; Presotto L; Bugiani O; Iannaccone S; Giaccone G; Tagliavini F; Perani D
[Ad] Address:Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy.
[Ti] Title:An In Vivo C-(R)-PK11195 PET and In Vitro Pathology Study of Microglia Activation in Creutzfeldt-Jakob Disease.
[So] Source:Mol Neurobiol;55(4):2856-2868, 2018 Apr.
[Is] ISSN:1559-1182
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Microgliosis is part of the immunobiology of Creutzfeldt-Jakob disease (CJD). This is the first report using C-(R)-PK11195 PET imaging in vivo to measure 18 kDa translocator protein (TSPO) expression, indexing microglia activation, in symptomatic CJD patients, followed by a postmortem neuropathology comparison. One genetic CJD (gCJD) patient, two sporadic CJD (sCJD) patients, one variant CJD (vCJD) patient (mean ± SD age, 47.50 ± 15.95 years), and nine healthy controls (mean ± SD age, 44.00 ± 11.10 years) were included in the study. TSPO binding potentials were estimated using clustering and parametric analyses of reference regions. Statistical comparisons were run at the regional and at the voxel-wise levels. Postmortem evaluation measured scrapie prion protein (PrP ) immunoreactivity, neuronal loss, spongiosis, astrogliosis, and microgliosis. C-(R)-PK11195-PET showed a significant TSPO overexpression at the cortical level in the two sCJD patients, as well as thalamic and cerebellar involvement; very limited parieto-occipital activation in the gCJD case; and significant increases at the subcortical level in the thalamus, basal ganglia, and midbrain and in the cerebellum in the vCJD brain. Along with misfolded prion deposits, neuropathology in all patients revealed neuronal loss, spongiosis and astrogliosis, and a diffuse cerebral and cerebellar microgliosis which was particularly dense in thalamic and basal ganglia structures in the vCJD brain. These findings confirm significant microgliosis in CJD, which was variably modulated in vivo and more diffuse at postmortem evaluation. Thus, TSPO overexpression in microglia activation, topography, and extent can vary in CJD subtypes, as shown in vivo, possibly related to the response to fast apoptotic processes, but reaches a large amount at the final disease course.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1704
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1007/s12035-017-0522-6

  6 / 7330 MEDLINE  
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[PMID]: 29310723
[Au] Autor:Cali I; Cohen ML; HaÑ—k S; Parchi P; Giaccone G; Collins SJ; Kofskey D; Wang H; McLean CA; Brandel JP; Privat N; Sazdovitch V; Duyckaerts C; Kitamoto T; Belay ED; Maddox RA; Tagliavini F; Pocchiari M; Leschek E; Appleby BS; Safar JG; Schonberger LB; Gambetti P
[Ad] Address:Departments of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, USA. ixc20@case.edu.
[Ti] Title:Iatrogenic Creutzfeldt-Jakob disease with Amyloid-ß pathology: an international study.
[So] Source:Acta Neuropathol Commun;6(1):5, 2018 01 08.
[Is] ISSN:2051-5960
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The presence of pathology related to the deposition of amyloid-ß (Aß) has been recently reported in iatrogenic Creutzfeldt-Jakob disease (iCJD) acquired from inoculation of growth hormone (GH) extracted from human cadaveric pituitary gland or use of cadaveric dura mater (DM) grafts.To investigate this phenomenon further, a cohort of 27 iCJD cases - 21 with adequate number of histopathological sections - originating from Australia, France, Italy, and the Unites States, were examined by immunohistochemistry, amyloid staining, and Western blot analysis of the scrapie prion protein (PrP ), and compared with age-group matched cases of sporadic CJD (sCJD), Alzheimer disease (AD) or free of neurodegenerative diseases (non-ND).Cases of iCJD and sCJD shared similar profiles of proteinase K-resistant PrP with the exception of iCJD harboring the "MMi" phenotype. Cerebral amyloid angiopathy (CAA), either associated with, or free of, Thioflavin S-positive amyloid core plaques (CP), was observed in 52% of 21 cases of iCJD, which comprised 37.5% and 61.5% of the cases of GH- and DM-iCJD, respectively. If only cases younger than 54 years were considered, Aß pathology affected 41%, 2% and 0% of iCJD, sCJD and non-ND, respectively. Despite the patients' younger age CAA was more severe in iCJD than sCJD, while Aß diffuse plaques, in absence of Aß CP, populated one third of sCJD. Aß pathology was by far most severe in AD. Tau pathology was scanty in iCJD and sCJD.In conclusion, (i) despite the divergences in the use of cadaveric GH and DM products, our cases combined with previous studies showed remarkably similar iCJD and Aß phenotypes indicating that the occurrence of Aß pathology in iCJD is a widespread phenomenon, (ii) CAA emerges as the hallmark of the Aß phenotype in iCJD since it is observed in nearly 90% of all iCJD with Aß pathology reported to date including ours, and it is shared by GH- and DM-iCJD, (iii) although the contributions to Aß pathology of other factors, including GH deficiency, cannot be discounted, our findings increase the mounting evidence that this pathology is acquired by a mechanism resembling that of prion diseases.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Em] Entry month:1801
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Process
[do] DOI:10.1186/s40478-017-0503-z

  7 / 7330 MEDLINE  
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[PMID]: 28449707
[Au] Autor:Llorens F; Thüne K; Sikorska B; Schmitz M; Tahir W; Fernández-Borges N; Cramm M; Gotzmann N; Carmona M; Streichenberger N; Michel U; Zafar S; Schuetz AL; Rajput A; Andréoletti O; Bonn S; Fischer A; Liberski PP; Torres JM; Ferrer I; Zerr I
[Ad] Address:Department of Neurology, University Medical Center Göttingen, and German Center for Neurodegenerative Diseases (DZNE), Robert Koch Strasse 40, 37075, Göttingen, Germany. franc.llorens@gmail.com.
[Ti] Title:Altered Ca homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease.
[So] Source:Acta Neuropathol Commun;5(1):35, 2017 04 27.
[Is] ISSN:2051-5960
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrP ). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca ) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca responsive genes in sCJD brain tissue, accompanied by two Ca -dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2. Pathogenic Calpain proteins activation in sCJD is linked to the cleavage of their cellular substrates, impaired autophagy and lysosomal damage, which is partially reversed by Calpain inhibition in a cellular prion model. Additionally, Calpain 1 treatment enhances seeding activity of PrP in a prion conversion assay. Neuronal lysosomal impairment caused by Calpain over activation leads to the release of the lysosomal protease Cathepsin S that in sCJD mainly localises in axons, although massive Cathepsin S overexpression is detected in microglial cells. Alterations in Ca homeostasis and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of the disease as detected in a humanized sCJD mouse model.Altogether our work indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor to the pathogenesis of sCJD at multiple molecular levels and a potential target for therapeutic intervention.
[Mh] MeSH terms primary: Brain/metabolism
Calcium/metabolism
Calpain/metabolism
Cathepsins/metabolism
Creutzfeldt-Jakob Syndrome/metabolism
Homeostasis/physiology
[Mh] MeSH terms secundary: Animals
Brain/pathology
Cations, Divalent/metabolism
Cells, Cultured
Creutzfeldt-Jakob Syndrome/pathology
Disease Models, Animal
Humans
Lysosomes/metabolism
Lysosomes/pathology
Mesocricetus
Mice, Transgenic
Neurons/metabolism
Neurons/pathology
PrPSc Proteins/metabolism
Rats, Wistar
Recombinant Proteins/metabolism
Sheep
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Cations, Divalent); 0 (PrPSc Proteins); 0 (Recombinant Proteins); EC 3.4.- (Cathepsins); EC 3.4.22.- (Calpain); SY7Q814VUP (Calcium)
[Em] Entry month:1712
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[Js] Journal subset:IM
[Da] Date of entry for processing:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s40478-017-0431-y

  8 / 7330 MEDLINE  
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[PMID]: 29486874
[Au] Autor:Cinar MU; Schneider DA; Waldron DF; O'Rourke KI; White SN
[Ad] Address:Department of Veterinary Microbiology and Pathology, Washington State University, 3003 ADBF, WSU, Pullman, WA 99164, USA; Erciyes University, Faculty of Agriculture, Department of Animal Science, Kayseri 38039, Turkey.
[Ti] Title:Goats singly heterozygous for PRNP S146 or K222 orally inoculated with classical scrapie at birth show no disease at ages well beyond 6 years.
[So] Source:Vet J;233:19-24, 2018 Mar.
[Is] ISSN:1532-2971
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Scrapie is a transmissible spongiform encephalopathy of sheep and goats, and scrapie eradication programs in many parts of the world rely on strong genetic resistance to classical scrapie in sheep. However, the utility of putative resistance alleles in goats has been a focus of research because goats can transmit scrapie to sheep and may serve as a scrapie reservoir. Prior work showed that disease-free survival time was significantly extended in orally inoculated goats singly heterozygous for prion amino acid substitutions S146 or K222, but average durations were only around 3 years post-inoculation. The aim of this study was to investigate whether extended survival would exceed 6 years, which represents the productive lifetimes of most commercial goats. While all control homozygotes were clinically affected by an average of <2 years, none of the NS146 or QK222 goats developed clinical scrapie or had PrP -positive rectal biopsies. Several NS146 and QK222 goats developed other conditions unrelated to scrapie, but tissue accumulation of PrP was not detected in any of these animals. The NS146 heterozygotes have remained disease-free for an average of 2734days (approximately 7.5 years), the longest duration of any classical scrapie challenge experiment with any genotype to date. The QK222 heterozygotes have remained disease-free for an average of 2450days (approximately 6.7 years), the longest reported average duration for QK222 goats challenged with classical scrapie. This research is ongoing, but the current results demonstrate S146 and K222 confer strong resistance to classical scrapie in goats.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180228
[Lr] Last revision date:180228
[St] Status:In-Data-Review

  9 / 7330 MEDLINE  
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[PMID]: 29422098
[Au] Autor:Huyben D; Boqvist S; Passoth V; Renström L; Allard Bengtsson U; Andréoletti O; Kiessling A; Lundh T; Vågsholm I
[Ad] Address:Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, 75007, Uppsala, Sweden. david.huyben@slu.se.
[Ti] Title:Screening of intact yeasts and cell extracts to reduce Scrapie prions during biotransformation of food waste.
[So] Source:Acta Vet Scand;60(1):9, 2018 Feb 08.
[Is] ISSN:1751-0147
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Yeasts can be used to convert organic food wastes to protein-rich animal feed in order to recapture nutrients. However, the reuse of animal-derived waste poses a risk for the transmission of infectious prions that can cause neurodegeneration and fatality in humans and animals. The aim of this study was to investigate the ability of yeasts to reduce prion activity during the biotransformation of waste substrates-thereby becoming a biosafety hurdle in such a circular food system. During pre-screening, 30 yeast isolates were spiked with Classical Scrapie prions and incubated for 72 h in casein substrate, as a waste substitute. Based on reduced Scrapie seeding activity, waste biotransformation and protease activities, intact cells and cell extracts of 10 yeasts were further tested. Prion analysis showed that five yeast species reduced Scrapie seeding activity by approximately 1 log10 or 90%. Cryptococcus laurentii showed the most potential to reduce prion activity since both intact and extracted cells reduced Scrapie by 1 log10 and achieved the highest protease activity. These results show that select forms of yeast can act as a prion hurdle during the biotransformation of waste. However, the limited ability of yeasts to reduce prion activity warrants caution as a sole barrier to transmission as higher log reductions are needed before using waste-cultured yeast in circular food systems.
[Mh] MeSH terms primary: Biotransformation
Prions/metabolism
Scrapie/prevention & control
Waste Management/methods
Yeasts/metabolism
[Mh] MeSH terms secundary: Animals
Cell Extracts/analysis
Food
Food Parasitology/standards
Food Parasitology/trends
Peptide Hydrolases/metabolism
Waste Management/standards
Yeasts/enzymology
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Cell Extracts); 0 (Prions); EC 3.4.- (Peptide Hydrolases)
[Em] Entry month:1802
[Cu] Class update date: 180227
[Lr] Last revision date:180227
[Js] Journal subset:IM
[Da] Date of entry for processing:180210
[St] Status:MEDLINE
[do] DOI:10.1186/s13028-018-0363-y

  10 / 7330 MEDLINE  
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[PMID]: 29338055
[Au] Autor:Mercer RCC; Daude N; Dorosh L; Fu ZL; Mays CE; Gapeshina H; Wohlgemuth SL; Acevedo-Morantes CY; Yang J; Cashman NR; Coulthart MB; Pearson DM; Joseph JT; Wille H; Safar JG; Jansen GH; Stepanova M; Sykes BD; Westaway D
[Ad] Address:Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada.
[Ti] Title:A novel Gerstmann-Sträussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles.
[So] Source:PLoS Pathog;14(1):e1006826, 2018 Jan.
[Is] ISSN:1553-7374
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP, the LGGLGGYV insertion also imparted alterations in PrP's unstructured N-terminus, resulting in a 16 kDa species following thermolysin exposure. This species comprises a plausible precursor to the 8 kDa PK-resistant fragment and its detection in adolescent Tg.HRdup mice suggests that an early start to accumulation could account for early disease of the index case. A 16 kDa thermolysin-resistant signature was also found in GSS patients with P102L, A117V, H187R and F198S alleles and has coordinates similar to GSS stop codon mutations. Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally distinct from that producing structural alterations in the C-terminus of PrP, as observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180213
[Lr] Last revision date:180213
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.ppat.1006826


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