{"title":"Novel method for classification of prion diseases by detecting PrPres signal patterns from formalin-fixed paraffin-embedded samples","authors":"Sachiko Koyama, Kaoru Yagita, Hideomi Hamasaki, Hideko Noguchi, Masahiro Shijo, Kosuke Matsuzono, Kei-Ichiro Takase, Keita Kai, Shin-Ichi Aishima, Kyoko Itoh, Toshiharu Ninomiya, Naokazu Sasagasako, Hiroyuki Honda","doi":"10.1080/19336896.2024.2337981","DOIUrl":"https://doi.org/10.1080/19336896.2024.2337981","url":null,"abstract":"Prion disease is an infectious and fatal neurodegenerative disease. Western blotting (WB)-based identification of proteinase K (PK)-resistant prion protein (PrPres) is considered a definitive diagn...","PeriodicalId":54585,"journal":{"name":"Prion","volume":"197 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140616697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PrionPub Date : 2023-12-01DOI: 10.1080/19336896.2023.2193128
Gregory D Sweetland, Connor Eggleston, Jason C Bartz, Candace K Mathiason, Anthony E Kincaid
{"title":"Expression of the cellular prion protein by mast cells in the human carotid body.","authors":"Gregory D Sweetland, Connor Eggleston, Jason C Bartz, Candace K Mathiason, Anthony E Kincaid","doi":"10.1080/19336896.2023.2193128","DOIUrl":"10.1080/19336896.2023.2193128","url":null,"abstract":"<p><p>Prion diseases are fatal neurologic disorders that can be transmitted by blood transfusion. The route for neuroinvasion following exposure to infected blood is not known. Carotid bodies (CBs) are specialized chemosensitive structures that detect the concentration of blood gasses and provide feedback for the neural control of respiration. Sensory cells of the CB are highly perfused and densely innervated by nerves that are synaptically connected to the brainstem and thoracic spinal cord, known to be areas of early prion deposition following oral infection. Given their direct exposure to blood and neural connections to central nervous system (CNS) areas involved in prion neuroinvasion, we sought to determine if there were cells in the human CB that express the cellular prion protein (PrP<sup>C</sup>), a characteristic that would support CBs serving as a route for prion neuroinvasion. We collected CBs from cadaver donor bodies and determined that mast cells located in the carotid bodies express PrP<sup>C</sup> and that these cells are in close proximity to blood vessels, nerves, and nerve terminals that are synaptically connected to the brainstem and spinal cord.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"17 1","pages":"67-74"},"PeriodicalIF":2.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10038025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9330776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PrionPub Date : 2023-12-01Epub Date: 2023-11-14DOI: 10.1080/19336896.2023.2276921
Dong-Lin Liang, Qi Shi, Kang Xiao, Ruhan A, Wei Zhou, Xiao-Ping Dong
{"title":"Two Chinese patients of sporadic Creutzfeldt-Jacob disease with a S97N mutation in <i>PRNP</i> gene.","authors":"Dong-Lin Liang, Qi Shi, Kang Xiao, Ruhan A, Wei Zhou, Xiao-Ping Dong","doi":"10.1080/19336896.2023.2276921","DOIUrl":"10.1080/19336896.2023.2276921","url":null,"abstract":"<p><p>Worldwide, 10-15% human prion disease are genetic and inherited, due to the special mutations or insertions in <i>PRNP</i> gene. Herein, we reported two Chinese patients with rapidly progressive dementia who were referred to the national Creutzfeldt-Jacob disease (CJD) surveillance as suspected CJD. Those two patients displayed sporadic CJD (sCJD)-like clinical phenotype, e.g. rapidly progressive dementia, visional and mental problems, sCJD-associated abnormalities in MRI. A missense mutation was identified in one <i>PRNP</i> allele of these two patients, resulting in a change from serine to asparagine at codon 97 (S97N). RT-QuIC of the cerebrospinal fluid samples from those two cases were positive. It indicates that they are very likely to be prion disease.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"17 1","pages":"141-144"},"PeriodicalIF":2.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PrionPub Date : 2022-12-01DOI: 10.1080/19336896.2022.2043077
Krista L Harrison, Sarah B Garrett, Joni Gilissen, Michael J Terranova, Alissa Bernstein Sideman, Christine S Ritchie, Michael D Geschwind
{"title":"Developing neuropalliative care for sporadic Creutzfeldt-Jakob Disease.","authors":"Krista L Harrison, Sarah B Garrett, Joni Gilissen, Michael J Terranova, Alissa Bernstein Sideman, Christine S Ritchie, Michael D Geschwind","doi":"10.1080/19336896.2022.2043077","DOIUrl":"10.1080/19336896.2022.2043077","url":null,"abstract":"<p><p>We aimed to identify targets for neuropalliative care interventions in sporadic Creutzfeldt-Jakob disease by examining characteristics of patients and sources of distress and support among former caregivers. We identified caregivers of decedents with sporadic Creutzfeldt-Jakob disease from the University of California San Francisco Rapidly Progressive Dementia research database. We purposively recruited 12 caregivers for in-depth interviews and extracted associated patient data. We analysed interviews using the constant comparison method and chart data using descriptive statistics. Patients had a median age of 70 (range: 60-86) years and disease duration of 14.5 months (range 4-41 months). Caregivers were interviewed a median of 22 (range 11-39) months after patient death and had a median age of 59 (range 45-73) years. Three major sources of distress included (1) the unique nature of sporadic Creutzfeldt-Jakob disease; (2) clinical care issues such as difficult diagnostic process, lack of expertise in sporadic Creutzfeldt-Jakob disease, gaps in clinical systems, and difficulties with end-of-life care; and (3) caregiving issues, including escalating responsibilities, intensifying stress, declining caregiver well-being, and care needs surpassing resources. Two sources of support were (1) clinical care, including guidance from providers about what to expect and supportive relationships; and (2) caregiving supports, including connection to persons with experience managing Creutzfeldt-Jakob disease, instrumental support, and social/emotional support. The challenges and supports described by caregivers align with neuropalliative approaches and can be used to develop interventions to address needs of persons with sporadic Creutzfeldt-Jakob disease and their caregivers.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"16 1","pages":"23-39"},"PeriodicalIF":1.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42444468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PrionPub Date : 2022-12-01DOI: 10.1080/19336896.2022.2095185
Andrea Bernardini, Gian Luigi Gigli, Francesco Janes, Gaia Pellitteri, Chiara Ciardi, Martina Fabris, Mariarosaria Valente
{"title":"Creutzfeldt-Jakob disease after COVID-19: infection-induced prion protein misfolding? A case report.","authors":"Andrea Bernardini, Gian Luigi Gigli, Francesco Janes, Gaia Pellitteri, Chiara Ciardi, Martina Fabris, Mariarosaria Valente","doi":"10.1080/19336896.2022.2095185","DOIUrl":"https://doi.org/10.1080/19336896.2022.2095185","url":null,"abstract":"<p><p>Creutzfeldt-Jakob disease (CJD) is a rare, fatal disease presenting with rapidly progressive neurological deficits caused by the accumulation of a misfolded form (PrPSc) of prion protein (PrPc). Coronavirus disease 2019 (COVID-19) is a primarily respiratory syndrome caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); many diverse neurological complications have been observed after COVID-19. We describe a young patient developing CJD two months after mild COVID-19. Presenting symptoms were visuospatial deficits and ataxia, evolving into a bedridden state with preserved consciousness and diffuse myoclonus. Diagnostic work-up was suggestive of CJD. The early age of onset and the short interval between respiratory and neurological symptoms might suggest a causal relationship: a COVID-19-related neuroinflammatory state may have induced the misfolding and subsequent aggregation of PrPSc. The present case emphasizes the link between neuroinflammation and protein misfolding. Further studies are needed to establish the role of SARS-CoV-2 as an initiator of neurodegeneration.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"16 1","pages":"78-83"},"PeriodicalIF":2.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10782687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PrionPub Date : 2022-12-01DOI: 10.1080/19336896.2022.2153551
Kyu Hwan Shim, Niti Sharma, Seong Soo A An
{"title":"Prion therapeutics: Lessons from the past.","authors":"Kyu Hwan Shim, Niti Sharma, Seong Soo A An","doi":"10.1080/19336896.2022.2153551","DOIUrl":"10.1080/19336896.2022.2153551","url":null,"abstract":"<p><p>Prion diseases are a group of incurable zoonotic neurodegenerative diseases (NDDs) in humans and other animals caused by the prion proteins. The abnormal folding and aggregation of the soluble cellular prion proteins (PrP<sup>C</sup>) into scrapie isoform (PrP<sup>Sc</sup>) in the Central nervous system (CNS) resulted in brain damage and other neurological symptoms. Different therapeutic approaches, including stalling PrP<sup>C</sup> to PrP<sup>Sc</sup> conversion, increasing PrP<sup>Sc</sup> removal, and PrP<sup>C</sup> stabilization, for which a spectrum of compounds, ranging from organic compounds to antibodies, have been explored. Additionally, a non-PrP targeted drug strategy using serpin inhibitors has been discussed. Despite numerous scaffolds being screened for anti-prion activity <i>in vitro</i>, only a few were effective <i>in vivo</i> and unfortunately, almost none of them proved effective in the clinical studies, most likely due to toxicity and lack of permeability. Recently, encouraging results from a prion-protein monoclonal antibody, PRN100, were presented in the first human trial on CJD patients, which gives a hope for better future for the discovery of other new molecules to treat prion diseases. In this comprehensive review, we have re-visited the history and discussed various classes of anti-prion agents, their structure, mode of action, and toxicity. Understanding pathogenesis would be vital for developing future treatments for prion diseases. Based on the outcomes of existing therapies, new anti-prion agents could be identified/synthesized/designed with reduced toxicity and increased bioavailability, which could probably be effective in treating prion diseases.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"16 1","pages":"265-294"},"PeriodicalIF":2.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9754114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10657281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Difference of geographic distributions of the Chinese patients with prion diseases in the permanent resident places and referring places.","authors":"Kang Xiao, Ming-Fan Pang, Yue-Qiao Zhao, Li-Ping Gao, Yue-Zhang Wu, Yuan Wang, Qi Shi, Xiao-Ping Dong","doi":"10.1080/19336896.2022.2080921","DOIUrl":"https://doi.org/10.1080/19336896.2022.2080921","url":null,"abstract":"<p><p>Human prion diseases (PrDs) are a group of transmissible neurodegenerative diseases that can be clarified as sporadic, genetic and iatrogenic forms. In this study, we have analysed the time and geographic distributions of 2011 PrD cases diagnosed by China National Surveillance for Creutzfeldt-Jakob disease (CNS-CJD) since 2006, including 1792 sporadic CJD (sCJD) cases and 219 gPrD cases. Apparently, the cases numbers of both sCJD and gPrD increased along with the surveillance years, showing a stepping up every five years. The geographic distributions of the PrDs cases based on the permanent residences were wide, distributing in 30 out of 31 provincial-level administrative divisions in Chinese mainland. However, the case numbers in the provincial level varied largely. The provinces in the eastern part of China had much more cases than those in the western part. Normalized the case numbers with the total population each province revealed higher incidences in six provinces. Further, the resident and referring places of all PrD cases were analysed, illustrating a clear concentrating pattern of referring in the large metropolises. Five provincial-level administrative divisions reported more PrD cases from other provinces than the local ones. Particularly, BJ reported not only more than one-fourth of all PrDs cases in Chinese mainland but also 3.64-fold more PrDs cases from other provinces than its local ones. We believed that good medical resources, well-trained programmes and knowledge of PrDs in the clinicians and the CDC staffs contributed to well-referring PrD cases in those large cities.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"16 1","pages":"58-65"},"PeriodicalIF":2.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10393198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PrionPub Date : 2022-12-01DOI: 10.1080/19336896.2022.2117535
Alberto F Fameli, Jessie Edson, Jeremiah E Banfield, Christopher S Rosenberry, W David Walter
{"title":"Variability in prion protein genotypes by spatial unit to inform susceptibility to chronic wasting disease.","authors":"Alberto F Fameli, Jessie Edson, Jeremiah E Banfield, Christopher S Rosenberry, W David Walter","doi":"10.1080/19336896.2022.2117535","DOIUrl":"https://doi.org/10.1080/19336896.2022.2117535","url":null,"abstract":"<p><p>Chronic wasting disease (CWD) is a fatal encephalopathy affecting North American cervids. Certain alleles in a host's prion protein gene are responsible for reduced susceptibility to CWD. We assessed for the first time variability in the prion protein gene of elk (<i>Cervus canadensis</i>) present in Pennsylvania, United States of America, a reintroduced population for which CWD cases have never been reported. We sequenced the prion protein gene (PRNP) of 565 elk samples collected over 7 years (2014-2020) and found two polymorphic sites (codon 21 and codon 132). The allele associated with reduced susceptibility to CWD is present in the population, and there was no evidence of deviations from Hardy-Weinberg equilibrium in any of our sampling years (<i>p</i>-values between 0.14 and 1), consistent with the lack of selective pressure on the PRNP. The less susceptible genotypes were found in a frequency similar to the ones reported for elk populations in the states of Wyoming and South Dakota before CWD was detected. We calculated the proportion of less susceptible genotypes in each hunt zone in Pennsylvania as a proxy for their vulnerability to the establishment of CWD, and interpolated these results to obtain a surface representing expected proportion of the less susceptible genotypes across the area. Based on this analysis, hunt zones located in the southern part of our study area have a low proportion of less susceptible genotypes, which is discouraging for elk persistence in Pennsylvania given that these hunt zones are adjacent to the deer Disease Management Area 3, where CWD has been present since 2014.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"16 1","pages":"254-264"},"PeriodicalIF":2.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10421581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A case of V180I genetic mutation Creutzfeldt Jakob disease (CJD) with delusional misidentification as an initial symptom.","authors":"Tomoyuki Nagata, Shunichiro Shinagawa, Nobuyuki Kobayashi, Kazuhiro Kondo, Masahiro Shigeta","doi":"10.1080/19336896.2021.2017701","DOIUrl":"https://doi.org/10.1080/19336896.2021.2017701","url":null,"abstract":"<p><p>An 84-year-old woman who had been diagnosed as having dementia with Lewy body (DLB) upon initial examination exhibited cognitive impairments and person delusional misidentification (DMS): she transiently claimed that her spouse was a stranger. She was re-examined at the age of 89 years; her frequency of speech and activities of daily living had both decreased, leading to verbal communication difficulties complicated by sensory aphasia, and brain diffusion-weighted (DW) magnetic resonance imaging (MRI) showed cortical hyperintensities in some areas of both hemispheres. About 4 months later, the DW high-intensity areas were observed to have expanded into diffuse cortical areas. While the clinical features of Creutzfeldt Jakob disease (CJD) (myoclonus; ataxia; parkinsonism; rapidly progressive cognitive impairments; periodic sharp discharges on electroencephalograms) were not observed, a genetic analysis of the prion protein (<i>PRNP</i>) gene, which was performed because of a family history of dementia, revealed a V180I mutation (heterozygosis: valine/isoleucine) suggesting genetic CJD (g-CJD). Her activity progressively decreased, reaching akinetic mutism about 11 months after the re-examination. Finally, she suffered from severe bedsores and died from aspiration pneumonia at the age of 90 years. The present report describes the first case of person DMS as an initial neuropsychiatric symptom for V180I g-CJD; the typical long-term clinical symptoms of CJD were not observed in this patient. The inclusion of person DMS as an initial clinical symptom and the presence of expansive cortical hyperintensity areas may be useful for clinicians attempting to diagnosis V180I g-CJD in patients with elusive symptoms.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"16 1","pages":"7-13"},"PeriodicalIF":2.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9757407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10655288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PrionPub Date : 2022-12-01DOI: 10.1080/19336896.2022.2095186
Yong-Chan Kim, Byung-Hoon Jeong
{"title":"Transcriptomic analysis identifies novel potential biomarkers and highlights cilium-related biological processes in the early stages of prion disease in mice.","authors":"Yong-Chan Kim, Byung-Hoon Jeong","doi":"10.1080/19336896.2022.2095186","DOIUrl":"https://doi.org/10.1080/19336896.2022.2095186","url":null,"abstract":"<p><p>Prion diseases are fatal and irreversible neurodegenerative diseases induced by the pathogenic form of the prion protein (PrP<sup>Sc</sup>), which is converted from the benign form of the prion protein (PrP<sup>C</sup>). These diseases are characterized by an extended asymptomatic incubation period accompanied by continuous conversion of PrP<sup>C</sup> to PrP<sup>Sc</sup>. However, to date, the mechanism governing the conversion to PrP<sup>Sc</sup> in the initial stages of prion disease has not been fully elucidated. We collected transcriptome data from the hippocampus of wild-type mice and prion-infected mice at 8 weeks post injection from the Gene Expression Omnibus and analysed differentially expressed genes and related signalling biological process using bioinformatic tools. We identified a total of 36 differentially expressed genes, including 22 upregulated genes and 14 downregulated genes. In addition, we identified that the cilium-related biological process was enriched in the early stages of prion disease. Furthermore, up- and down-regulated genes were associated with cilium-related cellular components and synapse-related cellular components, respectively. To the best of our knowledge, our study was the first to observe the upregulation of cilium-related genes in the early stages of prion disease.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"16 1","pages":"84-90"},"PeriodicalIF":2.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10782689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}