Prion最新文献

{"title":"Characterization of the prion protein gene in axis deer (<i>Axis axis</i>) and implications for susceptibility to chronic wasting disease.","authors":"Matthew J Buchholz,&nbsp;Emily A Wright,&nbsp;Blake A Grisham,&nbsp;Robert D Bradley,&nbsp;Thomas L Arsuffi,&nbsp;Warren C Conway","doi":"10.1080/19336896.2021.1910177","DOIUrl":"https://doi.org/10.1080/19336896.2021.1910177","url":null,"abstract":"<p><p>Axis deer (<i>Axis axis</i>) occur both in captivity and free-ranging populations in portions of North America, but to-date, no data exist pertaining to the species' susceptibility to CWD. We sequenced the prion protein gene (<i>PRNP</i>) from axis deer. We then compared axis deer PrP^C sequences and amino acid polymorphisms to those of CWD susceptible species. A single <i>PRNP</i> allele with no evidence of intraspecies variation was identified in axis deer that indicates axis deer <i>PRNP</i> is most similar to North American elk (<i>Cervus canadensis</i>) <i>PRNP</i>. Therefore, axis deer may be susceptible to CWD. We recommend proactively increasing CWD surveillance for axis deer, particularly where CWD has been detected and axis deer are sympatric with native North American CWD susceptible species.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"44-52"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2021.1910177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25574320","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":"Development of molecular tools for diagnosis of Alzheimer's disease that are based on detection of amyloidogenic proteins.","authors":"Konstantin Y Kulichikhin, Sergei A Fedotov, Maria S Rubel, Natalia M Zalutskaya, Anastasia E Zobnina, Oksana A Malikova, Nikolay G Neznanov, Yury O Chernoff, Aleksandr A Rubel","doi":"10.1080/19336896.2021.1917289","DOIUrl":"10.1080/19336896.2021.1917289","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common form of dementia that usually occurs among older people. AD results from neuronal degeneration that leads to the cognitive impairment and death. AD is incurable, typically develops over the course of many years and is accompanied by a loss of functional autonomy, making a patient completely dependent on family members and/or healthcare workers. Critical features of AD are pathological polymerization of Aβ peptide and microtubule-associated protein tau, accompanied by alterations of their conformations and resulting in accumulation of cross-β fibrils (amyloids) in human brains. AD apparently progresses asymptomatically for years or even decades before the appearance of symptoms. Therefore, development of the early AD diagnosis at a pre-symptomatic stage is essential for potential therapies. This review is focused on current and potential molecular tools (including non-invasive methods) that are based on detection of amyloidogenic proteins and can be applicable to early diagnosis of AD.<b>Abbreviations</b>: Aβ - amyloid-β peptide; AβO - amyloid-β oligomers; AD - Alzheimer's disease; ADRDA - Alzheimer's Disease and Related Disorders Association; APH1 - anterior pharynx defective 1; APP - amyloid precursor protein; BACE1 - β-site APP-cleaving enzyme 1; BBB - brain blood barrier; CJD - Creutzfeldt-Jakob disease; CRM - certified reference material; CSF - cerebrospinal fluid; ELISA - enzyme-linked immunosorbent assay; FGD - ¹⁸F-fluorodesoxyglucose (2-deoxy-2-[¹⁸F]fluoro-D-glucose); IP-MS - immunoprecipitation-mass spectrometry assay; MCI - mild cognitive impairment; MDS - multimer detection system; MRI - magnetic resonance imaging; NIA-AA - National Institute on Ageing and Alzheimer's Association; NINCDS - National Institute of Neurological and Communicative Disorders and Stroke; PEN2 - presenilin enhancer 2; PET - positron emission tomography; PiB - Pittsburgh Compound B; PiB-SUVR - PIB standardized uptake value ratio; PMCA - Protein Misfolding Cycling Amplification; PrP - Prion Protein; P-tau - hyperphosphorylated tau protein; RMP - reference measurement procedure; RT-QuIC - real-time quaking-induced conversion; SiMoA - single-molecule array; ThT - thioflavin T; TSEs - Transmissible Spongiform Encephslopathies; T-tau - total tau protein.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"56-69"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38916024","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":"PART and ARTAG tauopathies at a relatively young age as a concomitant finding in sporadic Creutzfeldt-Jakob disease.","authors":"Kateřina Menšíková,&nbsp;Radoslav Matěj,&nbsp;Eva Parobková,&nbsp;Magdalena Smětáková,&nbsp;Petr Kaňovský","doi":"10.1080/19336896.2021.1946378","DOIUrl":"https://doi.org/10.1080/19336896.2021.1946378","url":null,"abstract":"<p><p>Interactions between prion protein (PrP) and tau protein have long been discussed, especially in relation to the pathogenesis of neurodegenerative diseases. The presence of tauopathy in the genetic forms of Creutzfeldt-Jakob disease (CJD) brains is not uncommon. Molecular interactions between PrP and tau protein have been demonstrated in animal models; the role is attributed to the structural properties of misfolded isoform of the host-encoded prion protein (PrP^Sc) aggregates, especially amyloid, which contributes to the phosphorylation of tau protein, which is reflected in the frequent occurrence of tau pathology in inherited prion amyloidoses. The question is the relationship between PrP^Sc and hippocampal tau pathology without amyloid deposits (i.e. PART and ARTAG) in sporadic CJD (sCJD). The co-occurrence of these two proteinopathies in sCJD brains is quite rare. These pathological entities have been described in only a few cases of sCJD, all of them were older than 70 years. There have been speculations about the possibility of accelerating the course of pre-existing tauopathy or the possibility of accelerating the ageing process in the CJD brains. Here we present the clinical course and neuropathological findings of a patient with sCJD in whom the above mentioned tauopathies PART and ARTAG, considered to be typical for older age, were found as early as 58 years of age. According to the available information, this case represents an unusually early occurrence of age-related tauopathies not only in relation to sCJD, but also in general.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"138-142"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2021.1946378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39153263","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":"STXBP1 forms amyloid-like aggregates in rat brain and demonstrates amyloid properties in bacterial expression system.","authors":"A V Chirinskaite,&nbsp;V A Siniukova,&nbsp;M E Velizhanina,&nbsp;J V Sopova,&nbsp;T A Belashova,&nbsp;S P Zadorsky","doi":"10.1080/19336896.2021.1883980","DOIUrl":"https://doi.org/10.1080/19336896.2021.1883980","url":null,"abstract":"<p><p>Amyloids are the fibrillar protein aggregates with cross-β structure. Traditionally amyloids were associated with pathology, however, nowadays more data is emerging about functional amyloids playing essential roles in cellular processes. We conducted screening for functional amyloids in rat brain. One of the identified proteins was STXBP1 taking part in vesicular transport and neurotransmitter secretion. Using SDD-AGE and protein fractionation we found out that STXBP1 forms small detergent-insoluble aggregates in rat brain. With immunoprecipitation analysis and C-DAG system, we showed that STXBP1 forms amyloid-like fibrils. Thus, STXBP1 demonstrates amyloid properties in rat brain and in bacterial expression system.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"29-36"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2021.1883980","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25372209","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":"Genetic Creutzfeldt-Jakob disease shows fatal family insomnia phenotype.","authors":"Bin Chen,&nbsp;Shan Zhang,&nbsp;Ying Xiao,&nbsp;Yingman Wu,&nbsp;Weiting Tang,&nbsp;Limin Yan,&nbsp;Zhengxue Zhang,&nbsp;Shengquan Qin,&nbsp;Mingming Dai,&nbsp;Yong You","doi":"10.1080/19336896.2021.1968291","DOIUrl":"https://doi.org/10.1080/19336896.2021.1968291","url":null,"abstract":"<p><p>We report a case of genetic Creutzfeldt-Jakob disease (gCJD), which has a clinical phenotype that is highly similar to Fatal Family Insomnia (FFI) and has a triad of Wernicke-Korsakoff syndrome (WKs) at the developmental stage of the disease. The 51-year-old male complained of sleep disorder and imbalance who had visited five different hospitals before diagnosed. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk, and memory disturbances. The disturbances increased during the course of the disease, which led to the death of the patient 18 months after the appearance of the signs. Although the patient show negative in brain magnetic resonance imaging (MRI) and 14-3-3 protein of cerebrospinal fluid (CSF), he was finally diagnosed with gCJD disease by the human prion protein (PRNP) gene mutations.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"177-182"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bc/a8/KPRN_15_1968291.PMC8425754.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39387114","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":"Upregulation of brain hepcidin in prion diseases.","authors":"Suman Chaudhary,&nbsp;Ajay Ashok,&nbsp;Aaron S Wise,&nbsp;Neil A Rana,&nbsp;Dallas McDonald,&nbsp;Alexander E Kritikos,&nbsp;Qingzhong Kong,&nbsp;Neena Singh","doi":"10.1080/19336896.2021.1946377","DOIUrl":"10.1080/19336896.2021.1946377","url":null,"abstract":"<p><p>Accumulation of redox-active iron in human sporadic Creutzfeldt-Jakob disease (sCJD) brain tissue and scrapie-infected mouse brains has been demonstrated previously. Here, we explored whether upregulation of local hepcidin secreted within the brain is the underlying cause of iron accumulation and associated toxicity. Using scrapie-infected mouse brains, we demonstrate transcriptional upregulation of hepcidin relative to controls. As a result, ferroportin (Fpn), the downstream effector of hepcidin and the only known iron export protein was downregulated, and ferritin, an iron storage protein was upregulated, suggesting increased intracellular iron. A similar transcriptional and translational upregulation of hepcidin, and decreased expression of Fpn and an increase in ferritin expression was observed in sCJD brain tissue. Further evaluation in human neuroblastoma cells (M17) exposed to synthetic mini-hepcidin showed downregulation of Fpn, upregulation of ferritin, and an increase in reactive oxygen species (ROS), resulting in cytotoxicity in a dose-dependent manner. Similar effects were noted in primary neurons isolated from mouse brain. As in M17 cells, primary neurons accumulated ferritin and ROS, and showed toxicity at five times lower concentration of mini-hepcidin. These observations suggest that upregulation of brain hepcidin plays a significant role in iron accumulation and associated neurotoxicity in human and animal prion disorders.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"126-137"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2021.1946377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39152120","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":"Detection of two dissimilar chronic wasting disease isolates in two captive Rocky Mountain elk (<i>Cervus canadensis</i>) herds.","authors":"Tracy A Nichols,&nbsp;Eric M Nicholson,&nbsp;Yihui Liu,&nbsp;Wanyun Tao,&nbsp;Terry R Spraker,&nbsp;Michael Lavelle,&nbsp;Justin Fischer,&nbsp;Qingzhong Kong,&nbsp;Kurt C VerCauteren","doi":"10.1080/19336896.2021.1982333","DOIUrl":"https://doi.org/10.1080/19336896.2021.1982333","url":null,"abstract":"<p><p>Chronic wasting disease (CWD) continues to spread in both wild and captive cervid herds in North America and has now been identified in wild reindeer and moose in Norway, Finland and Sweden. There is limited knowledge about the variety and characteristics of isolates or strains of CWD that exist in the landscape and their implications on wild and captive cervid herds. In this study, we evaluated brain samples from two captive elk herds that had differing prevalence, history and timelines of CWD incidence. Site 1 had a 16-year history of CWD with a consistently low prevalence between 5% and 10%. Twelve of fourteen naïve animals placed on the site remained CWD negative after 5 years of residence. Site 2 herd had a nearly 40-year known history of CWD with long-term environmental accrual of prion leading to nearly 100% of naïve animals developing clinical CWD within two to 12 years. Obex samples of several elk from each site were compared for CWD prion strain deposition, genotype in prion protein gene codon 132, and conformational stability of CWD prions. CWD prions in the obex from site 2 had a lower conformational stability than those from site 1, which was independent of prnp genotype at codon 132. These findings suggest the existence of different CWD isolates between the two sites and suggest potential differential disease attack rates for different CWD strains.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"207-215"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8682864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39731301","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":"Epitope-specific anti-PrP antibody toxicity: a comparative <i>in-silico</i> study of human and mouse prion proteins.","authors":"Utpal Kumar Adhikari,&nbsp;Mourad Tayebi","doi":"10.1080/19336896.2021.1964326","DOIUrl":"https://doi.org/10.1080/19336896.2021.1964326","url":null,"abstract":"<p><p>Despite having therapeutic potential, anti-PrP antibodies caused a major controversy due to their neurotoxic effects. For instance, treating mice with ICSM antibodies delayed prion disease onset, but both were found to be either toxic or innocuous to neurons by researchers following cross-linking PrP^C. In order to elucidate and understand the reasons that led to these contradictory outcomes, we conducted a comprehensive <i>in silico</i> study to assess the antibody-specific toxicity. Since most therapeutic anti-PrP antibodies were generated against human truncated recombinant PrP^91-231 or full-length mouse PrP^23-231, we reasoned that host specificity (human vs murine) of PrP^C might influence the nature of the specific epitopes recognized by these antibodies at the structural level possibly explaining the 'toxicity' discrepancies reported previously. Initially, molecular dynamics simulation and pro-motif analysis of full-length human (hu)PrP and mouse (mo)PrP 3D structure displayed conspicuous structural differences between huPrP and moPrP. We identified 10 huPrP and 6 moPrP linear B-cell epitopes from the prion protein 3D structure where 5 out of 10 huPrP and 3 out of 6 moPrP B-cell epitopes were predicted to be potentially toxic in immunoinformatics approaches. Herein, we demonstrate that some of the predicted potentially 'toxic' epitopes identified by the <i>in silico</i> analysis were similar to the epitopes recognized by the toxic antibodies such as ICSM18 (146-159), POM1 (138-147), D18 (133-157), ICSM35 (91-110), D13 (95-103) and POM3 (95-100). This <i>in silico</i> study reveals the role of host specificity of PrP^C in epitope-specific anti-PrP antibody toxicity.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"155-176"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/99/KPRN_15_1964326.PMC8900626.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39504517","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":"Monomeric a-synuclein (aS) inhibits amyloidogenesis of human prion protein (hPrP) by forming a stable aS-hPrP hetero-dimer.","authors":"Satoshi Yamashita,&nbsp;Yuji O Kamatari,&nbsp;Ryo Honda,&nbsp;Ayumi Niwa,&nbsp;Hiroyuki Tomiata,&nbsp;Akira Hara,&nbsp;Kazuo Kuwata","doi":"10.1080/19336896.2021.1910176","DOIUrl":"https://doi.org/10.1080/19336896.2021.1910176","url":null,"abstract":"<p><p>Intermolecular interaction between hPrP and αS was investigated using high-speed atomic force microscopy, dynamic light scattering, and nuclear magnetic resonance. We found that hPrP spontaneously gathered and naturally formed oligomers. Upon addition of monomer αS with a disordered conformation, poly-dispersive property of hPrP was lost, and hetero-dimer formation started quite coherently, and further oligomerization was not observed. Solution structure of hPrP-αS dimer was firstly characterized using hetero-nuclear NMR spectroscopy. In this hetero-dimeric complex, C-terminal helical region of hPrP was in the molten-globule like state, while specific sites including hot spot and C-terminal region of αS selectively interacted with hPrP. Thus αS may suppress amyloidogenesis of hPrP by trapping the hPrP intermediate by the formation of a stable hetero-dimer with hPrP.<b>Abbreviations:</b> hPrP, human prion protein of amino acid residues of 23-231; PrP^C, cellular form of prion protein; PrP^Sc, scrapie form of prion protein, HS-AFM; high speed atomic force microscopy; αS, α-synuclein; DLS, dynamic light scattering.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"37-43"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2021.1910176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25585874","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":"Prion domains as a driving force for the assembly of functional nanomaterials.","authors":"Weiqiang Wang,&nbsp;Salvador Ventura","doi":"10.1080/19336896.2020.1785659","DOIUrl":"https://doi.org/10.1080/19336896.2020.1785659","url":null,"abstract":"ABSTRACT Amyloids display a highly ordered fibrillar structure. Many of these assemblies appear associated with human disease. However, the controllable, stable, tunable, and robust nature of amyloid fibrils can be exploited to build up remarkable nanomaterials with a wide range of applications in biomedicine and biotechnology. Functional prions constitute a particular class of amyloids. These transmissible proteins exhibit a modular architecture, with a disordered prion domain responsible for the assembly and one or more globular domains that account for the activity. Importantly, the original globular protein can be replaced with any protein of interest, without compromising the fibrillation potential. These genetic fusions form fibrils in which the globular domain remains folded, rendering functional nanostructures. However, in some cases, steric hindrance restricts the activity of these fibrils. This limitation can be solved by dissecting prion domains into shorter sequences that keep their self-assembling properties while allowing better access to the active protein in the fibrillar state. In this review, we will discuss the properties of prion-like functional nanomaterials and the amazing applications of these biocompatible fibrillar arrangements.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"14 1","pages":"170-179"},"PeriodicalIF":2.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2020.1785659","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10637767","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}