Publications

heat shock protein 70 selectively mediates the degradation of cytosolic prps and restores the cytosolic prp-induced cytotoxicity via a molecular interaction.	although the aggregation of prpsc is thought to be crucial for the neuropathology of prion diseases, there is evidence in cultured cells and transgenic mice that neuronal death can be triggered by the accumulation of cytosolic prps, leading to the hypothesis that the accumulation of prps in the cytosol of neurons may be a primary neurotoxic culprit. hsp70, a molecular chaperone involved in protein folding/refolding and degradation in the cytoplasm, has a protective effect in some models of neuro ...	2012	23216755
acetone precipitation of the scrapie agent results in successful recovery of prp(sc) but decreased infectivity.	bioassay is considered the most sensitive method for evaluating prion inactivation procedures. because prions are resistant to methods effective at inactivating conventional microorganisms, prion inactivation research has focused on relatively harsh alternatives, such as concentrated sodium hypochlorite or sodium hydroxide. often, bioassay for residual infectivity in these studies requires dilution or biochemical alteration of the treated sample in order to maintain subject health and survival. ...	2012	22519670
soil-mediated prion transmission: is local soil-type a key determinant of prion disease incidence?	prion diseases, including chronic wasting disease (cwd) and scrapie, can be transmitted via indirect environmental routes. animals habitually ingest soil, and results from laboratory experiments demonstrate prions can bind to a wide range of soils and soil minerals, retain the ability to replicate, and remain infectious, indicating soil could serve as a reservoir for natural prion transmission and a potential prion exposure route for humans. preliminary epidemiological modeling suggests soil tex ...	2012	22265680
assessing prion infectivity of human urine in sporadic creutzfeldt-jakob disease.	prion diseases are neurodegenerative conditions associated with a misfolded and infectious protein, scrapie prion protein (prp(sc)). prp(sc) propagate prion diseases within and between species and thus pose risks to public health. prion infectivity or prp(sc) presence has been demonstrated in urine of experimentally infected animals, but there are no recent studies of urine from patients with creutzfeldt-jakob disease (cjd). we performed bioassays in transgenic mice expressing human prp to asses ...	2012	22260924
selection of distinct strain phenotypes in mice infected by ovine natural scrapie isolates similar to ch1641 experimental scrapie.	abstract: a few cases of transmissible spongiform encephalopathies in sheep have been described in france in which the protease-resistant prion protein (prp) exhibited some features in western blot of experimental bovine spongiform encephalopathy in sheep. their molecular characteristics were indistinguishable from those produced in the ch1641 experimental scrapie isolate. four of these ch1641-like isolates were inoculated intracerebrally into wild-type c57bl/6 mice. in striking contrast to prev ...	2012	22249459
time course of prion seeding activity in cerebrospinal fluid of scrapie-infected hamsters after intratongue and intracerebral inoculations.	to assess prospects for early diagnosis of prion disease based on prion seeding activity in cerebrospinal fluid (csf), we measured the activity over time in scrapie-infected hamsters by real-time quaking-induced conversion (rt-quic). after intracerebral inoculation, activity appeared in csf within 1 day and plateaued weeks before the onset of clinical signs. however, after intratongue inoculation, activity first appeared in csf with the onset of clinical signs, well after higher-level accumulati ...	2012	22238438
prion protein polymerisation triggered by manganese-generated prion protein seeds.	prion diseases are neurodegenerative diseases that can be transmitted between individuals. the exact cause of these diseases remains unknown. however, one of the key events associates with the disease is the aggregation of a cellular protein, the prion protein. the mechanism of this is still unclear. however, it is likely that the aggregation is trigged by a seeding mechanism in which an oligomer of the prion protein is able to catalyse polymerisation of further prion protein into larger aggrega ...	2012	22007749
in vitro prion protein conversion suggests risk of bighorn sheep (ovis canadensis) to transmissible spongiform encephalopathies.	transmissible spongiform encephalopathies (tses) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; cwd). the geographical range of bighorn sheep (ovis canadensis; bhs) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of cwd in cervids. no tses have been documented in bhs, but the susceptibility of this species to tses remains unknown.	2013	23938169
removal of tse agent from plasma products manufactured in the united kingdom.	the outbreak of vcjd in the uk leads to concern regarding the potential for human-to-human transmission of this agent. plasma-derived products such as albumin, immunoglobulin and coagulation factors were manufactured by bpl from uk plasma up until 1999 when a switch to us plasma was made. in the current study, the capacity of various manufacturing processes that were in use both prior to and after this time to remove the tse agent was tested.	2013	23170907
a bayesian framework to assess the potential for controlling classical scrapie in sheep flocks using a live diagnostic test.	current strategies to control classical scrapie remove animals at risk of scrapie rather than those known to be infected with the scrapie agent. advances in diagnostic tests, however, suggest that a more targeted approach involving the application of a rapid live test may be feasible in future. here we consider the use of two diagnostic tests: recto-anal mucosa-associated lymphatic tissue (ramalt) biopsies; and a blood-based assay. to assess their impact we developed a stochastic age- and prion ...	2013	24021519
three-dimensional reconstruction of the pharyngeal tonsil innervation pattern in sheep.	the pharyngeal tonsil has recently been identified as a new participant in airborne contamination by the ovine scrapie agent. in the context of scrapie pathogenesis, we conducted a three-dimensional reconstruction of the innervation pattern in the lymphoid compartments of this tonsil. this model confirmed that very few nerve fibres penetrated the lymphoid follicles and suggested that the nerve fibre distribution in the interfollicular and subepithelial areas is more suitable with neuro-invasion ...	2013	23932773
evaluation of a combinatorial approach to prion inactivation using an oxidizing agent, sds, and proteinase k.	prions demonstrate an unusual resistance to methods effective at inactivating conventional microorganisms. this has resulted in a very tangible and difficult infection control challenge to the medical and veterinary communities, as well as animal agriculture and related industries. currently accepted practices of harsh chemical treatments such as prolonged exposure to sodium hydroxide or sodium hypochlorite, or autoclaving are not suitable in many situations. less caustic and more readily applic ...	2013	23886483
prion protein: structural features and related toxicity.	transmissible spongiform encephalopathies, or prion diseases, is a group of infectious neurodegenerative disorders. the conformational conversion from cellular form (prp(c)) to disease-causing isoform (prp(sc)) is considered to be the most important and remarkable event in these diseases, while accumulation of prp(sc) is thought to be the main reason for cell death, inflammation and spongiform degeneration observed in infected individuals. although these rare but unique neurodegenerative disorde ...	2013	23615535
abnormal activation of microglia accompanied with disrupted cx3cr1/cx3cl1 pathway in the brains of the hamsters infected with scrapie agent 263k.	microglial cells are resident mononuclear phagocytes of the central nervous system (cns). active proliferation of microglia in the brain has been identified in neurodegenerative disorders, including some kinds of prion disease. however, the detailed regional distribution between microglia and prp(sc) deposition has not been presented, and investigation of fractalkine signaling which is involved in the regulation of activation of microglia in prion disease is not well documented. in this study, t ...	2013	23526370
role of cd40 in prion disease and the immune response to recombinant prp.	the cd40 receptor-cd40 ligand (cd40-cd40l) interaction has been shown to affect both immune and non-immune cells and is implicated in diverse activities including immunoglobulin class switching (igm to igg), atherosclerosis, chronic inflammation and alzheimer's disease pathogenesis. a number of groups have studied the role of cd40 in prion disease, however, the results are conflicting presumably due to the use of different scrapie agent-host strain combinations and routes of infection. in the cu ...	2013	23419881
exposure of rml scrapie agent to a sodium percarbonate-based product and sodium dodecyl sulfate renders prpsc protease sensitive but does not eliminate infectivity.	prions, the causative agents of the transmissible spongiform encephalopathies, are notoriously difficult to inactivate. current decontamination recommendations by the world health organization include prolonged exposure to 1 n sodium hydroxide or > 20,000 ppm sodium hypochlorite, or autoclaving. for decontamination of large stainless steel surfaces and equipment as in abattoirs, for example, these methods are harsh or unsuitable. the current study was designed to evaluate the effectiveness of a ...	2013	23311930
abnormally upregulated αb-crystallin was highly coincidental with the astrogliosis in the brains of scrapie-infected hamsters and human patients with prion diseases.	αb-crystallin is a member of the small heat shock protein family constitutively presenting in brains at a relatively low level. to address the alteration of αb-crystallin in prion disease, the αb-crystallin levels in the brains of scrapie agent 263 k-infected hamsters were analyzed. the levels of αb-crystallin were remarkably increased in the brains of 263 k-infected hamsters, showing a time-dependent manner along with incubation time. immunohistochemical (ihc) and immunofluorescent (ifa) assays ...	2013	23832485
prp octarepeats region determined the interaction with caveolin-1 and phosphorylation of caveolin-1 and fyn.	caveolin-1 is one of the major constituents of caveolae. both cav-1 and prp are plasma membrane proteins, which show active capacities for molecular interactions with many other proteins or agents, including themselves. using yeast two-hybrid system and immunoprecipitation, we reconfirmed the molecular interaction between human cav-1 and prp. with co-immunoprecipitation tests, prp(c)-cav-1 and prp(sc)-cav-1 complexes were identified in the brain homogenates of normal and scrapie agent 263k-infec ...	2013	23283514
infection of prions and treatment of prp106-126 alter the endogenous status of protein 14-3-3 and trigger the mitochondrial apoptosis possibly via activating bax pathway.	the 14-3-3 proteins are a family of highly homologous and ubiquitously expressed isoforms that are involved in a wide variety of physiological processes. 14-3-3 have showed actively molecular interaction with prp and positive 14-3-3 is frequently observed in the cerebrospinal fluid (csf) samples of the patients with sporadic creutzfeldt-jakob disease (cjd). however, the alterations of 14-3-3 in the brain tissues of patients with prion diseases remain little addressed. to address the possible cha ...	2014	24135906
lack of prion accumulation in lymphoid tissues of prnp arq/arr sheep intracranially inoculated with the agent of scrapie.	sheep scrapie is a transmissible spongiform encephalopathy that can be transmitted horizontally. the prion protein gene (prnp) profoundly influences the susceptibility of sheep to the scrapie agent and the tissue levels and distribution of prpsc in affected sheep. the purpose of this study was to compare the survival time and prpsc tissue distribution in sheep with highly resistant and highly susceptible prnp genotypes after intracranial inoculation of the agent of scrapie. five sheep each of ge ...	2014	25233232
remarkable reductions of paks in the brain tissues of scrapie-infected rodent possibly linked closely with neuron loss.	prion diseases are irreversible progressive neurodegenerative diseases characterized in the brain by prp(sc) deposits, neuronal degeneration, gliosis and by cognitive, behavioral and physical impairments, leading to severe incapacity and inevitable death. proteins of the p21-activated kinase (pak) family are noted for roles in gene transcription, cytoskeletal dynamics, cell cycle progression and survival signaling. in the present study, we aimed to identify the potential roles of paks during pri ...	2014	24870058
apparent reduction of adam10 in scrapie-infected cultured cells and in the brains of scrapie-infected rodents.	it has been described that a disintegrin and metalloproteinase (adam10) may involve in the physiopathology of prion diseases, but the direct molecular basis still remains unsolved. in this study, we confirmed that adam10 was able to cleave recombinant human prion protein in vitro. using immunoprecipitation tests (ip) and immunofluorescent assays (ifa), reliable molecular interaction between the native cellular form of prp (prp(c)) and adam10 was observed not only in various cultured neuronal cel ...	2014	24771043
disruption of glycosylation enhances ubiquitin-mediated proteasomal degradation of shadoo in scrapie-infected rodents and cultured cells.	shadoo (sho) is an n-glycosylated glycophosphatidylinositol-anchored protein that is expressed in the brain and exhibits neuroprotective properties. recently, research has shown that a reduction of sho levels may reflect the presence of prpsc in the brain. however, the possible mechanism by which prion infection triggers down-regulation of sho remains unclear. in the present study, western blot and immunohistochemical assays revealed that sho, especially glycosylated sho, declined markedly in th ...	2014	24390475
interaction between 14-3-3β and prp influences the dimerization of 14-3-3 and fibrillization of prp106-126.	proteins of the 14-3-3 family are universal participate in multiple cellular processes. however, their exact role in the pathogenesis of prion diseases remains unclear. in this study, we proposed that human prp was able to form molecular complex with 14-3-3β. the domains responsible for the interactions between prp and 14-3-3β were mapped at the segments of amino acid (aa) residues 106-126 within prp and aa 1-38 within 14-3-3β. homology modeling revealed that the key aa residues for molecular in ...	2014	24269782
(1)h nmr brain metabonomics of scrapie exposed sheep.	while neurochemical metabolite modifications, determined by different techniques, have been diffusely reported in human and mice brains affected by transmissible spongiform encephalopathies (tses), this aspect has been little studied in the natural animal hosts with the same pathological conditions so far. herein, we investigated, by high resolution (1)h nmr spectroscopy and multivariate statistical data analysis, the brain metabolite profile of sheep exposed to a scrapie agent in a naturally af ...	2015	25959287
fbxw7-induced mtor degradation forces autophagy to counteract persistent prion infection.	autophagy is an important protein degradation pathway and a part of the innate immune system that is activated in the brain tissue during animal and human prion diseases. however, the possible mechanism by which prion infection triggers autophagy and the significance of activated autophagy on prion accumulation remain unknown. here, we demonstrated that autophagic flux was enhanced in the persistent prion-infected cell line, smb-s15. knockdown of atg5 and the presence of three autophagic inhibit ...	2016	25579381
overexpression of plk3 mediates the degradation of abnormal prion proteins dependent on chaperone-mediated autophagy.	polo-like kinase 3 (plk3) is the main cause of cell cycle reentry-related neuronal apoptosis which has been implicated in the pathogenesis of prion diseases. previous work also showed the regulatory activity of exogenous plk3 on the degradation of prp (prion protein) mutants and pathogenic prp(sc); however, the precise mechanisms remain unknown. in this study, we identified that the overexpression of plk3-mediated degradation of prp mutant and prp(sc) was repressed by lysosome rather than by pro ...	2016	27344333
the priority position paper: protecting europe's food chain from prions.	bovine spongiform encephalopathy (bse) created a global european crisis in the 1980s and 90s, with very serious health and economic implications. classical bse now appears to be under control, to a great extent as a result of a global research effort that identified the sources of prions in meat and bone meal (mbm) and developed new animal-testing tools that guided policy. priority ( www.prionpriority.eu ) was a european union (eu) framework program 7 (fp7)-funded project through which 21 europe ...	2016	27220820
oral inoculation of neonatal suffolk sheep with the agent of classical scrapie results in prp(sc) accumulation in sheep with the prnp arq/arq but not the arq/arr genotype.	scrapie is a transmissible spongiform encephalopathy that can be transmitted amongst susceptible sheep. the prion protein gene (prnp) profoundly influences the susceptibility of sheep to the scrapie agent. this study reports the failure to detect prp(sc) in nervous or lymphoid tissues of suffolk sheep of the prnp arq/arr genotype after oral inoculation with a u.s. scrapie isolate. lambs were inoculated within the first 24 h of birth with 1 ml of a 10% (wt./vol.) brain homogenate derived from a c ...	2016	27033930
evidence of scrapie transmission to sheep via goat milk.	previous studies confirmed that classical scrapie can be transmitted via milk in sheep. the current study aimed to investigate whether scrapie can also be transmitted via goat milk using in vivo (new-born lambs fed milk from scrapie-affected goats due to the unavailability of goat kids from guaranteed scrapie-free herds) and in vitro methods (serial protein misfolding cyclic amplification [spmca] on milk samples).	2016	27640200
the brain no levels and nos activities ascended in the early and middle stages and descended in the terminal stage in scrapie-infected animal models.	the infections of prion agents may cause progressive and fatal neurodegenerative diseases in humans and a serial of animal species. previous studies have proposed that the levels of nitric oxide (no) and nitric oxide synthase (nos) in the brains of some neurodegeneration diseases changed, while s-nitrosylation (sno) of many brain proteins altered in prion diseases. to elucidate the potential changes of brain no levels during prion infection, the no levels and nos activities in the brain tissues ...	2017	26887380
a heparin purification process removes spiked transmissible spongiform encephalopathy agent.	in 2000, bovine heparin was withdrawn from the us market for fear of contamination with bovine spongiform encephalopathy (bse) agent, the cause of variant creutzfeldt-jakob disease in humans. thus, us heparin is currently sourced only from pig intestines. availability of alternative sources of crude heparin, a life-saving drug, would benefit public health. bovine heparin is an obvious option, but bse clearance by the bovine heparin manufacturing process should be evaluated. to this end, using ha ...	2017	28116677
prion protein and genetic susceptibility to diseases caused by its misfolding.	early genetic studies on scrapie, an infectious neurodegenerative disease of sheep that was adapted to mice, provided evidence in support of the hypothesis that the agent was a slow virus with a nucleic acid genome independent of the host. particularly compelling support for an independent genome came from the existence of strains of scrapie agent, some of which were true breeding, while others appeared to mutate under selective pressure. kuru, a neurodegenerative disease in the remote highlands ...	2017	28838658
reduction of nf-κb (p65) in scrapie-infected cultured cells and in the brains of scrapie-infected rodents.	transcription factor nf-κb functions as a pleiotropic regulator of target genes controlling physiological function as well as pathological processes of many different diseases, including some neurodegenerative diseases. however, the role of nf-κb in the pathogenesis of prion disease remains ambiguous. in this study, the status of nf-κb (p65) in a prion-infected cell line smb-s15 was first evaluated. significantly lower levels of p65 and the phosphorylated form of p65 (p-p65) were detected in smb ...	2017	28783945