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  1 / 806 MEDLINE  
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[PMID]:28464931
[Au] Autor:Wulf MA; Senatore A; Aguzzi A
[Ad] Endereço:Institute of Neuropathology, University of Zurich, Rämistrasse 100, CH-8091, Zürich, Switzerland.
[Ti] Título:The biological function of the cellular prion protein: an update.
[So] Source:BMC Biol;15(1):34, 2017 05 02.
[Is] ISSN:1741-7007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The misfolding of the cellular prion protein (PrP ) causes fatal neurodegenerative diseases. Yet PrP is highly conserved in mammals, suggesting that it exerts beneficial functions preventing its evolutionary elimination. Ablation of PrP in mice results in well-defined structural and functional alterations in the peripheral nervous system. Many additional phenotypes were ascribed to the lack of PrP , but some of these were found to arise from genetic artifacts of the underlying mouse models. Here, we revisit the proposed physiological roles of PrP in the central and peripheral nervous systems and highlight the need for their critical reassessment using new, rigorously controlled animal models.
[Mh] Termos MeSH primário: Sistema Nervoso Central/patologia
Sistema Nervoso Periférico/patologia
Doenças Priônicas/metabolismo
Proteínas Priônicas/metabolismo
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Camundongos
Doenças Priônicas/etiologia
Proteínas Priônicas/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Prion Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1186/s12915-017-0375-5


  2 / 806 MEDLINE  
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[PMID]:29261664
[Au] Autor:Zamponi E; Buratti F; Cataldi G; Caicedo HH; Song Y; Jungbauer LM; LaDu MJ; Bisbal M; Lorenzo A; Ma J; Helguera PR; Morfini GA; Brady ST; Pigino GF
[Ad] Endereço:Laboratorio de Neuropatología Experimental, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina.
[Ti] Título:Prion protein inhibits fast axonal transport through a mechanism involving casein kinase 2.
[So] Source:PLoS One;12(12):e0188340, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prion diseases include a number of progressive neuropathies involving conformational changes in cellular prion protein (PrPc) that may be fatal sporadic, familial or infectious. Pathological evidence indicated that neurons affected in prion diseases follow a dying-back pattern of degeneration. However, specific cellular processes affected by PrPc that explain such a pattern have not yet been identified. Results from cell biological and pharmacological experiments in isolated squid axoplasm and primary cultured neurons reveal inhibition of fast axonal transport (FAT) as a novel toxic effect elicited by PrPc. Pharmacological, biochemical and cell biological experiments further indicate this toxic effect involves casein kinase 2 (CK2) activation, providing a molecular basis for the toxic effect of PrPc on FAT. CK2 was found to phosphorylate and inhibit light chain subunits of the major motor protein conventional kinesin. Collectively, these findings suggest CK2 as a novel therapeutic target to prevent the gradual loss of neuronal connectivity that characterizes prion diseases.
[Mh] Termos MeSH primário: Transporte Axonal/fisiologia
Axônios/metabolismo
Caseína Quinase II/metabolismo
Proteínas Priônicas/fisiologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Hipocampo/citologia
Hipocampo/metabolismo
Cinesina/metabolismo
Camundongos
Mitocôndrias/metabolismo
Fosforilação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Prion Proteins); EC 2.7.11.1 (Casein Kinase II); EC 3.6.4.4 (Kinesin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188340


  3 / 806 MEDLINE  
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[PMID]:29187684
[Au] Autor:Watanabe M; Matsumoto Y; Okamoto K; Okuda B; Mizuta I; Mizuno T
[Ad] Endereço:Department of Neurology, Ehime Prefectural Central Hospital.
[Ti] Título:[A case of hereditary sensory and autonomic neuropathy type 1E with frontal lobe dysfunction as an initial symptom].
[So] Source:Rinsho Shinkeigaku;57(12):753-758, 2017 Dec 27.
[Is] ISSN:1882-0654
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:A 49-year-old man had developed gradually personality change, gait disturbance, and hearing loss for five years. On admission, he presented with frontal release signs, stuttering, vertical gaze palsy, sensorineural deafness, muscle rigidity, ataxia, and sensory disturbance with areflexia in the lower extremities. Brain MRI demonstrated atrophy in the cerebellum and midbrain tegmentum as well as cerebral atrophy, predominantly in the frontal lobe. He was tentatively diagnosed as progressive supranuclear palsy on the basis of clinical features and imagings. On nerve conduction study, no sensory nerve action potentials were elicited in the upper and lower extremities. Details of family history revealed a hereditary sensory neuropathy with autosomal dominant inheritance in his relatives. Because genetic analysis showed a rare missense mutation (c.1483T>C, p.Y495H) in DNA methyltransferase 1 gene, we diagnosed him as having hereditary sensory and autonomic neuropathy type 1E (HSAN1E). In addition, p.M232R mutation in prion protein gene was detected. It should be kept in mind that there are some patients with HSAN1E presenting with frontal lobe dysfunction as an initial symptom and with clinical features mimicking progressive supranuclear palsy.
[Mh] Termos MeSH primário: Neuropatias Hereditárias Sensoriais e Autônomas/diagnóstico
Neuropatias Hereditárias Sensoriais e Autônomas/genética
[Mh] Termos MeSH secundário: Atrofia
Encéfalo/patologia
DNA (Citosina-5-)-Metiltransferase 1/genética
Diagnóstico Diferencial
Lobo Frontal
Neuropatias Hereditárias Sensoriais e Autônomas/patologia
Neuropatias Hereditárias Sensoriais e Autônomas/fisiopatologia
Seres Humanos
Masculino
Meia-Idade
Mutação
Proteínas Priônicas/genética
Paralisia Supranuclear Progressiva
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Prion Proteins); EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1); EC 2.1.1.37 (DNMT1 protein, human)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.5692/clinicalneurol.cn-001043


  4 / 806 MEDLINE  
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[PMID]:29220360
[Au] Autor:Eigenbrod S; Frick P; Bertsch U; Mitteregger-Kretzschmar G; Mielke J; Maringer M; Piening N; Hepp A; Daude N; Windl O; Levin J; Giese A; Sakthivelu V; Tatzelt J; Kretzschmar H; Westaway D
[Ad] Endereço:Center for Neuropathology and Prion Research, Ludwig Maximilians University, Munich, Germany.
[Ti] Título:Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice.
[So] Source:PLoS One;12(12):e0188989, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1-4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt) controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G) mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain.
[Mh] Termos MeSH primário: Histidina/química
Proteínas Priônicas/química
Scrapie/patologia
[Mh] Termos MeSH secundário: Animais
Camundongos
Camundongos Transgênicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Prion Proteins); 4QD397987E (Histidine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188989


  5 / 806 MEDLINE  
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[PMID]:29058651
[Au] Autor:Haley NJ; Rielinger R; Davenport KA; O'Rourke K; Mitchell G; Richt JA
[Ad] Endereço:1​Department of Microbiology and Immunology, Midwestern University, Glendale, AZ, USA.
[Ti] Título:Estimating chronic wasting disease susceptibility in cervids using real-time quaking-induced conversion.
[So] Source:J Gen Virol;98(11):2882-2892, 2017 Nov.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In mammals, susceptibility to prion infection is primarily modulated by the host's cellular prion protein (PrP ) sequence. In the sheep scrapie model, a graded scale of susceptibility has been established both in vivo and in vitro based on PrP amino acids 136, 154 and 171, leading to global breeding programmes to reduce the prevalence of scrapie in sheep. Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrP allele conferring absolute resistance in cervids has been identified. To model the susceptibility of various naturally occurring and hypothetical cervid PrP alleles in vitro, we compared the amplification rates and amyloid extension efficiencies of eight distinct CWD isolates in recombinant cervid PrP substrates using real-time quaking-induced conversion. We hypothesized that the in vitro conversion characteristics of these isolates in cervid substrates would correlate to in vivo susceptibility - permitting susceptibility prediction for the rare alleles found in nature. We also predicted that hypothetical alleles with multiple resistance-associated codons would be more resistant to in vitro conversion than natural alleles with a single resistant codon. Our studies demonstrate that in vitro conversion metrics align with in vivo susceptibility, and that alleles with multiple amino acid substitutions, each influencing resistance independently, do not necessarily contribute additively to conversion resistance. Importantly, we found that the naturally occurring whitetail deer QGAK substrate exhibited the slowest amplification rate among those evaluated, suggesting that further investigation of this allele and its resistance in vivo is warranted.
[Mh] Termos MeSH primário: Cervos
Predisposição Genética para Doença
Proteínas Priônicas/genética
Doença de Emaciação Crônica/genética
[Mh] Termos MeSH secundário: Alelos
Amiloide/metabolismo
Animais
Agregação Patológica de Proteínas
Doença de Emaciação Crônica/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid); 0 (Prion Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171024
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000952


  6 / 806 MEDLINE  
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[PMID]:28934337
[Au] Autor:Teruya K; Oguma A; Nishizawa K; Kamitakahara H; Doh-Ura K
[Ad] Endereço:Department of Neurochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
[Ti] Título:Pyrene conjugation and spectroscopic analysis of hydroxypropyl methylcellulose compounds successfully demonstrated a local dielectric difference associated with in vivo anti-prion activity.
[So] Source:PLoS One;12(9):e0185357, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Our previous study on prion-infected rodents revealed that hydroxypropyl methylcellulose compounds (HPMCs) with different molecular weights but similar composition and degree of substitution have different levels of long-lasting anti-prion activity. In this study, we searched these HPMCs for a parameter specifically associated with in vivo anti-prion activity by analyzing in vitro chemical properties and in vivo tissue distributions. Infrared spectroscopic and thermal analyses revealed no differences among HPMCs, whereas pyrene conjugation and spectroscopic analysis revealed that the fluorescence intensity ratio of peak III/peak I correlated with anti-prion activity. This correlation was more clearly demonstrated in the anti-prion activity of the 1-year pre-infection treatment than that of the immediate post-infection treatment. In addition, the intensity ratio of peak III/peak I negatively correlated with the macrophage uptake level of HPMCs in our previous study. However, the in vivo distribution pattern was apparently not associated with anti-prion activity and was different in the representative tissues. These findings suggest that pyrene conjugation and spectroscopic analysis are powerful methods to successfully demonstrate local dielectric differences in HPMCs and provide a feasible parameter denoting the long-lasting anti-prion activity of HPMCs in vivo.
[Mh] Termos MeSH primário: Derivados da Hipromelose/química
Derivados da Hipromelose/farmacologia
Proteínas Priônicas/antagonistas & inibidores
Pirenos/química
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
Encéfalo/efeitos dos fármacos
Encéfalo/metabolismo
Impedância Elétrica
Derivados da Hipromelose/metabolismo
Derivados da Hipromelose/farmacocinética
Macrófagos/metabolismo
Camundongos
Peso Molecular
Proteínas Priônicas/metabolismo
Espectroscopia de Infravermelho com Transformada de Fourier
Baço/efeitos dos fármacos
Baço/metabolismo
Relação Estrutura-Atividade
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Prion Proteins); 0 (Pyrenes); 3NXW29V3WO (Hypromellose Derivatives); 9E0T7WFW93 (pyrene)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185357


  7 / 806 MEDLINE  
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[PMID]:28922846
[Au] Autor:Honda H; Sasaki K; Takashima H; Mori D; Koyama S; Suzuki SO; Iwaki T
[Ad] Endereço:Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Higashi-Ku, Fukuoka, Japan; Department of Neurology, Saga-Ken Medical Centre Koseikan, Saga, Japan; Department of Pathology, Saga-Ken Medical Centre Koseikan, Saga, Japan.
[Ti] Título:Different Complicated Brain Pathologies in Monozygotic Twins With Gerstmann-Sträussler-Scheinker Disease.
[So] Source:J Neuropathol Exp Neurol;76(10):854-863, 2017 Oct 01.
[Is] ISSN:1554-6578
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal, dominantly inherited prion disease. In this study, we present different complicated brain pathologies determined postmortem of monozygotic GSS twin sisters. Case 1 showed cerebellar ataxia at the age of 58 years, and died at 66 years. Case 2 became symptomatic at the age of 75 years, and died at 79 years. There was a 17-year difference in the age of onset between the twins. Postmortem examination revealed numerous prion protein (PrP) plaques in the brains of both cases. The spongiform change and brain atrophy in case 1 were more severe compared with those in case 2. Western-blot analysis identified proteinase-resistant PrP (PrPres) at the molecular weight of 21-30 kDa and 8 kDa in the twins. Gel filtration revealed that PrPres was mainly composed of PrP oligomer. PrPres signal patterns were similar between the twins. Additionally, case 1 showed α-synucleinopathy and case 2 showed Alzheimer disease pathology. These different proteinopathies were involved in the amyloid plaque formations of both cases. The degree of GSS pathology was mainly related to disease duration. The amyloid plaque formations could be decorated by concomitant neuropathological changes such as α-synucleinopathy and tauopathy.
[Mh] Termos MeSH primário: Doença de Alzheimer/complicações
Encéfalo/patologia
Doença de Gerstmann-Straussler-Scheinker/complicações
Doença de Gerstmann-Straussler-Scheinker/patologia
[Mh] Termos MeSH secundário: Idoso
Autopsia
Encéfalo/metabolismo
Feminino
Doença de Gerstmann-Straussler-Scheinker/genética
Seres Humanos
Placa Amiloide/etiologia
Placa Amiloide/patologia
Proteínas PrPSc/metabolismo
Proteínas Priônicas/metabolismo
Sinucleínas/metabolismo
Gêmeos Monozigóticos
[Pt] Tipo de publicação:JOURNAL ARTICLE; TWIN STUDY
[Nm] Nome de substância:
0 (PrPSc Proteins); 0 (Prion Proteins); 0 (Synucleins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnen/nlx068


  8 / 806 MEDLINE  
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[PMID]:28910420
[Au] Autor:Groveman BR; Raymond GJ; Campbell KJ; Race B; Raymond LD; Hughson AG; Orrú CD; Kraus A; Phillips K; Caughey B
[Ad] Endereço:Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
[Ti] Título:Role of the central lysine cluster and scrapie templating in the transmissibility of synthetic prion protein aggregates.
[So] Source:PLoS Pathog;13(9):e1006623, 2017 Sep.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mammalian prion structures and replication mechanisms are poorly understood. Most synthetic recombinant prion protein (rPrP) amyloids prepared without cofactors are non-infectious or much less infectious than bona fide tissue-derived PrPSc. This effect has been associated with differences in folding of the aggregates, manifested in part by reduced solvent exclusion and protease-resistance in rPrP amyloids, especially within residues ~90-160. Substitution of 4 lysines within residues 101-110 of rPrP (central lysine cluster) with alanines (K4A) or asparagines (K4N) allows formation of aggregates with extended proteinase K (PK) resistant cores reminiscent of PrPSc, particularly when seeded with PrPSc. Here we have compared the infectivity of rPrP aggregates made with K4N, K4A or wild-type (WT) rPrP, after seeding with scrapie brain homogenate (ScBH) or normal brain homogenate (NBH). None of these preparations caused clinical disease on first passage into rodents. However, the ScBH-seeded fibrils (only) led to a subclinical pathogenesis as indicated by increases in prion seeding activity, neuropathology, and abnormal PrP in the brain. Seeding activities usually accumulated to much higher levels in animals inoculated with ScBH-seeded fibrils made with the K4N, rather than WT, rPrP molecules. Brain homogenates from subclinical animals induced clinical disease on second passage into "hamsterized" Tg7 mice, with shorter incubation times in animals inoculated with ScBH-seeded K4N rPrP fibrils. On second passage from animals inoculated with ScBH-seeded WT fibrils, we detected an additional PK resistant PrP fragment that was similar to that of bona fide PrPSc. Together these data indicate that both the central lysine cluster and scrapie seeding of rPrP aggregates influence the induction of PrP misfolding, neuropathology and clinical manifestations upon passage in vivo. We confirm that some rPrP aggregates can initiate further aggregation without typical pathogenesis in vivo. We also provide evidence that there is little, if any, biohazard associated with routine RT-QuIC assays.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
Lisina/metabolismo
Proteínas Priônicas/metabolismo
Scrapie/metabolismo
[Mh] Termos MeSH secundário: Amiloide/química
Animais
Encéfalo/patologia
Endopeptidase K/metabolismo
Camundongos Transgênicos
Proteínas PrPSc/metabolismo
Agregados Proteicos/fisiologia
Proteínas Recombinantes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid); 0 (PrPSc Proteins); 0 (Prion Proteins); 0 (Protein Aggregates); 0 (Recombinant Proteins); EC 3.4.21.64 (Endopeptidase K); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006623


  9 / 806 MEDLINE  
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[PMID]:28880938
[Au] Autor:Davenport KA; Hoover CE; Bian J; Telling GC; Mathiason CK; Hoover EA
[Ad] Endereço:Prion Research Center, Microbiology, Immunology and Pathology Department, Colorado State University, Fort Collins, Colorado, United States of America.
[Ti] Título:PrPC expression and prion seeding activity in the alimentary tract and lymphoid tissue of deer.
[So] Source:PLoS One;12(9):e0183927, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The agent responsible for prion diseases is a misfolded form of a normal protein (PrPC). The prion hypothesis stipulates that PrPC must be present for the disease to manifest. Cervid populations across the world are infected with chronic wasting disease, a horizontally-transmissible prion disease that is likely spread via oral exposure to infectious prions (PrPCWD). Though PrPCWD has been identified in many tissues, there has been little effort to characterize the overall PrPC expression in cervids and its relationship to PrPCWD accumulation. We used immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay to describe PrPC expression in naïve white-tailed deer. We used real-time, quaking-induced conversion (RT-QuIC) to detect prion seeding activity in CWD-infected deer. We assessed tissues comprising the alimentary tract, alimentary-associated lymphoid tissue and systemic lymphoid tissue from 5 naïve deer. PrPC was expressed in all tissues, though expression was often very low compared to the level in the CNS. IHC identified specific cell types wherein PrPC expression is very high. To compare the distribution of PrPC to PrPCWD, we examined 5 deer with advanced CWD infection. Using RT-QuIC, we detected prion seeding activity in all 21 tissues. In 3 subclinical deer sacrificed 4 months post-inoculation, we detected PrPCWD consistently in alimentary-associated lymphoid tissue, irregularly in alimentary tract tissues, and not at all in the brain. Contrary to our hypothesis that PrPC levels dictate prion accumulation, PrPC expression was higher in the lower gastrointestinal tissues than in the alimentary-associated lymphoid system and was higher in salivary glands than in the oropharyngeal lymphoid tissue. These data suggest that PrPC expression is not the sole driver of prion accumulation and that alimentary tract tissues accumulate prions before centrifugal spread from the brain occurs.
[Mh] Termos MeSH primário: Cervos/metabolismo
Trato Gastrointestinal/metabolismo
Tecido Linfoide/metabolismo
Proteínas Priônicas/metabolismo
[Mh] Termos MeSH secundário: Animais
Western Blotting
Ensaio de Imunoadsorção Enzimática
Epitélio/metabolismo
Imuno-Histoquímica
Tecido Nervoso/metabolismo
Doença de Emaciação Crônica/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Prion Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183927


  10 / 806 MEDLINE  
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[PMID]:28878088
[Au] Autor:Papasavva-Stylianou P; Simmons MM; Ortiz-Pelaez A; Windl O; Spiropoulos J; Georgiadou S
[Ad] Endereço:Veterinary Services, Nicosia, Cyprus.
[Ti] Título:Effect of Polymorphisms at Codon 146 of the Goat PRNP Gene on Susceptibility to Challenge with Classical Scrapie by Different Routes.
[So] Source:J Virol;91(22), 2017 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This report presents the results of experimental challenges of goats with scrapie by both the intracerebral (i.c.) and oral routes, exploring the effects of polymorphisms at codon 146 of the goat gene on resistance to disease. The results of these studies illustrate that while goats of all genotypes can be infected by i.c. challenge, the survival distribution of the animals homozygous for asparagine at codon 146 was significantly shorter than those of animals of all other genotypes (chi-square value, 10.8; = 0.001). In contrast, only those animals homozygous for asparagine at codon 146 (NN animals) succumbed to oral challenge. The results also indicate that any cases of infection in non-NN animals can be detected by the current confirmatory test (immunohistochemistry), although successful detection with the rapid enzyme-linked immunosorbent assay (ELISA) was more variable and dependent on the polymorphism. Together with data from previous studies of goats exposed to infection in the field, these data support the previously reported observations that polymorphisms at this codon have a profound effect on susceptibility to disease. It is concluded that only animals homozygous for asparagine at codon 146 succumb to scrapie under natural conditions. In goats, like in sheep, there are PRNP polymorphisms that are associated with susceptibility or resistance to scrapie. However, in contrast to the polymorphisms in sheep, they are more numerous in goats and may be restricted to certain breeds or geographical regions. Therefore, eradication programs must be specifically designed depending on the identification of suitable polymorphisms. An initial analysis of surveillance data suggested that such a polymorphism in Cypriot goats may lie in codon 146. In this study, we demonstrate experimentally that NN animals are highly susceptible after i.c. inoculation. The presence of a D or S residue prolonged incubation periods significantly, and prions were detected in peripheral tissues only in NN animals. In oral challenges, prions were detected only in NN animals, and the presence of a D or S residue at this position conferred resistance to the disease. This study provides an experimental transmission model for assessing the genetic susceptibility of goats to scrapie.
[Mh] Termos MeSH primário: Substituição de Aminoácidos
Códon
Predisposição Genética para Doença
Cabras/genética
Polimorfismo Genético
Proteínas Priônicas/genética
Scrapie/genética
[Mh] Termos MeSH secundário: Animais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon); 0 (Prion Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE



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