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PART and ARTAG tauopathies at a relatively young age as a concomitant finding in sporadic Creutzfeldt-Jakob disease. PART和ARTAG病变在相对年轻的年龄作为散发性克雅氏病的伴随发现。
IF 2.3 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-12-01 DOI: 10.1080/19336896.2021.1946378
Kateřina Menšíková, Radoslav Matěj, Eva Parobková, Magdalena Smětáková, Petr Kaňovský

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 (PrPSc) 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 PrPSc 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.

朊蛋白(PrP)和tau蛋白之间的相互作用一直被讨论,特别是与神经退行性疾病的发病机制有关。Creutzfeldt-Jakob病(CJD)大脑的遗传形式中存在牛头病并不罕见。PrP和tau蛋白之间的分子相互作用已在动物模型中得到证实;这一作用归因于宿主编码的朊蛋白(PrPSc)聚集体,特别是淀粉样蛋白的错误折叠异构体的结构特性,它有助于tau蛋白的磷酸化,这反映在遗传性朊蛋白淀粉样病中经常发生tau病理。问题是PrPSc与散发性CJD (sCJD)中无淀粉样蛋白沉积(即PART和ARTAG)的海马tau病理之间的关系。这两种蛋白病变在sCJD脑中同时出现是非常罕见的。这些病理实体仅在少数sCJD病例中被描述,所有病例均大于70岁。人们一直在猜测,这可能会加速已经存在的牛头病的进程,也可能会加速克雅氏症患者大脑的衰老过程。在这里,我们报告了一例sCJD患者的临床过程和神经病理学结果,该患者早在58岁时就发现了上述病变PART和ARTAG,这些病变被认为是老年人的典型症状。根据现有信息,该病例不仅与sCJD有关,而且与一般情况有关,代表了年龄相关的牛头病变的异常早期发生。
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引用次数: 0
STXBP1 forms amyloid-like aggregates in rat brain and demonstrates amyloid properties in bacterial expression system. STXBP1在大鼠脑内形成淀粉样聚集体,并在细菌表达系统中表现出淀粉样特性。
IF 2.3 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-12-01 DOI: 10.1080/19336896.2021.1883980
A V Chirinskaite, V A Siniukova, M E Velizhanina, J V Sopova, T A Belashova, S P Zadorsky

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.

淀粉样蛋白是具有交叉β结构的纤维蛋白聚集体。传统上,淀粉样蛋白与病理有关,然而,现在越来越多的数据显示,功能性淀粉样蛋白在细胞过程中起着重要作用。我们对大鼠脑内的功能性淀粉样蛋白进行了筛选。其中一个被鉴定的蛋白是STXBP1,参与水疱转运和神经递质分泌。通过sds - age和蛋白分离,我们发现STXBP1在大鼠脑内形成小的洗涤剂不溶性聚集体。通过免疫沉淀分析和C-DAG系统,我们发现STXBP1形成淀粉样原纤维。因此,STXBP1在大鼠脑和细菌表达系统中表现出淀粉样蛋白特性。
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引用次数: 3
Genetic Creutzfeldt-Jakob disease shows fatal family insomnia phenotype. 遗传性克雅氏病显示致死性家族性失眠表型。
IF 2.3 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-12-01 DOI: 10.1080/19336896.2021.1968291
Bin Chen, Shan Zhang, Ying Xiao, Yingman Wu, Weiting Tang, Limin Yan, Zhengxue Zhang, Shengquan Qin, Mingming Dai, Yong You

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.

我们报告一例遗传性克雅氏病(gCJD),其临床表型与致死性家族失眠症(FFI)高度相似,并且在疾病的发育阶段具有Wernicke-Korsakoff综合征(WKs)的三联征。这名51岁的男性自诉睡眠障碍和失衡,在确诊前曾去过5家不同的医院。神经学检查显示了WKs的三种典型症状,如凝视性麻痹、四肢和躯干共济失调以及记忆障碍。在疾病过程中,这些干扰增加,导致患者在症状出现18个月后死亡。虽然患者脑磁共振成像(MRI)和脑脊液14-3-3蛋白检测结果均为阴性,但经人朊蛋白(PRNP)基因突变,最终诊断为gCJD。
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引用次数: 3
Upregulation of brain hepcidin in prion diseases. 脑hepcidin在朊病毒疾病中的上调。
IF 2.3 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-12-01 DOI: 10.1080/19336896.2021.1946377
Suman Chaudhary, Ajay Ashok, Aaron S Wise, Neil A Rana, Dallas McDonald, Alexander E Kritikos, Qingzhong Kong, Neena Singh

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.

氧化还原活性铁在人类散发性克雅氏病(sCJD)脑组织和感染瘙痒病的小鼠大脑中的积累已被证实。在这里,我们探讨了脑内分泌的局部铁调素的上调是否是铁积聚和相关毒性的根本原因。使用感染瘙痒的小鼠大脑,我们证明了铁调素相对于对照的转录上调。结果,铁调素的下游效应子、唯一已知的铁输出蛋白ferroportin(Fpn)下调,铁储存蛋白Ferrobin上调,表明细胞内铁增加。在sCJD脑组织中观察到类似的铁调素转录和翻译上调、Fpn表达减少和铁蛋白表达增加。在暴露于合成的迷你铁调素的人类神经母细胞瘤细胞(M17)中的进一步评估显示,Fpn下调,铁蛋白上调,活性氧(ROS)增加,导致细胞毒性呈剂量依赖性。在从小鼠大脑分离的初级神经元中也观察到了类似的作用。与M17细胞一样,原代神经元积累铁蛋白和ROS,并在低5倍浓度的微量铁调素下表现出毒性。这些观察结果表明,脑铁调素的上调在人类和动物朊病毒疾病中的铁积累和相关神经毒性中起着重要作用。
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引用次数: 4
Detection of two dissimilar chronic wasting disease isolates in two captive Rocky Mountain elk (Cervus canadensis) herds. 两个圈养的落基山麋鹿群中两种不同的慢性消耗性疾病分离株的检测。
IF 2.3 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-12-01 DOI: 10.1080/19336896.2021.1982333
Tracy A Nichols, Eric M Nicholson, Yihui Liu, Wanyun Tao, Terry R Spraker, Michael Lavelle, Justin Fischer, Qingzhong Kong, Kurt C VerCauteren

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.

慢性消耗性疾病(CWD)继续在北美的野生和圈养鹿群中传播,目前已在挪威、芬兰和瑞典的野生驯鹿和驼鹿中发现。目前对存在于景观中的CWD分离株或菌株的种类和特征及其对野生和圈养鹿群的影响的了解有限。在这项研究中,我们评估了两个圈养麋鹿群的大脑样本,这些麋鹿群具有不同的CWD发病率、历史和发病时间。站点1有16年的CWD病史,患病率一直在5% - 10%之间。在该地点放置的14只naïve动物中,有12只在居住5年后仍呈CWD阴性。站点2畜群有近40年的已知CWD病史,长期的朊病毒环境累积导致naïve动物在2至12年内几乎100%发生临床CWD。比较了每个站点的几个麋鹿样本的CWD朊病毒菌株沉积,朊病毒蛋白基因密码子132的基因型以及CWD朊病毒的构象稳定性。CWD朊病毒的构象稳定性较低,与密码子132上的prnp基因型无关。这些发现表明两个地点存在不同的CWD分离株,并提示不同CWD菌株的潜在不同疾病发病率。
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引用次数: 2
Epitope-specific anti-PrP antibody toxicity: a comparative in-silico study of human and mouse prion proteins. 表位特异性抗prp抗体毒性:人类和小鼠朊病毒蛋白的比较计算机研究。
IF 2.3 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-12-01 DOI: 10.1080/19336896.2021.1964326
Utpal Kumar Adhikari, Mourad Tayebi

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 PrPC. In order to elucidate and understand the reasons that led to these contradictory outcomes, we conducted a comprehensive in silico study to assess the antibody-specific toxicity. Since most therapeutic anti-PrP antibodies were generated against human truncated recombinant PrP91-231 or full-length mouse PrP23-231, we reasoned that host specificity (human vs murine) of PrPC 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 in silico 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 in silico study reveals the role of host specificity of PrPC in epitope-specific anti-PrP antibody toxicity.

尽管具有治疗潜力,但抗prp抗体由于其神经毒性作用而引起了重大争议。例如,用ICSM抗体治疗小鼠延缓了朊病毒疾病的发病,但是研究人员在交叉连接PrPC后发现,这两种抗体对神经元要么有毒,要么无害。为了阐明和理解导致这些相互矛盾的结果的原因,我们进行了一项全面的计算机研究来评估抗体特异性毒性。由于大多数治疗性抗prp抗体是针对人类截断重组PrP91-231或全长小鼠PrP23-231产生的,我们推断,PrPC的宿主特异性(人与小鼠)可能会影响这些抗体在结构水平上识别的特异性表位的性质,这可能解释了之前报道的“毒性”差异。首先,对人(hu)PrP和小鼠(mo)PrP的全长三维结构进行分子动力学模拟和前基序分析,发现huPrP和moPrP在结构上存在显著差异。我们从朊病毒蛋白3D结构中鉴定出10个huPrP和6个moPrP线性b细胞表位,其中10个huPrP和6个moPrP b细胞表位中有5个在免疫信息学方法中被预测为潜在毒性。在此,我们证明了通过硅分析识别的一些预测的潜在“毒性”表位与有毒抗体如ICSM18(146-159)、POM1(138-147)、D18(133-157)、ICSM35(91-110)、D13(95-103)和POM3(95-100)识别的表位相似。这项计算机研究揭示了宿主特异性PrPC在表位特异性抗prp抗体毒性中的作用。
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引用次数: 0
Monomeric a-synuclein (aS) inhibits amyloidogenesis of human prion protein (hPrP) by forming a stable aS-hPrP hetero-dimer. 单体a-synuclein (aS)通过形成稳定的aS-hPrP异二聚体抑制人朊蛋白(hPrP)淀粉样蛋白的形成。
IF 2.3 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-12-01 DOI: 10.1080/19336896.2021.1910176
Satoshi Yamashita, Yuji O Kamatari, Ryo Honda, Ayumi Niwa, Hiroyuki Tomiata, Akira Hara, Kazuo Kuwata

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.Abbreviations: hPrP, human prion protein of amino acid residues of 23-231; PrPC, cellular form of prion protein; PrPSc, scrapie form of prion protein, HS-AFM; high speed atomic force microscopy; αS, α-synuclein; DLS, dynamic light scattering.

利用高速原子力显微镜、动态光散射和核磁共振研究了hPrP与αS的分子间相互作用。我们发现hPrP自发聚集并自然形成低聚物。当无序构象的单体αS加入后,hPrP的多色散特性丧失,异质二聚体的形成开始较为一致,未发生进一步的寡聚反应。利用异核磁共振波谱首次表征了hPrP-αS二聚体的溶液结构。在该异质二聚体配合物中,hPrP的c端螺旋区处于熔融球状状态,而αS的热点和c端区等特定位点与hPrP选择性相互作用。因此,αS可能通过与hPrP形成稳定的异二聚体来捕获hPrP中间体,从而抑制hPrP的淀粉样变性。缩写:hPrP,人朊蛋白的氨基酸残基为23-231;PrPC,朊病毒蛋白的细胞形式;PrPSc,痒样朊蛋白,HS-AFM;高速原子力显微镜;α,α-核蛋白;动态光散射。
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引用次数: 2
Prion domains as a driving force for the assembly of functional nanomaterials. 朊病毒结构域作为功能纳米材料组装的驱动力。
IF 2.3 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1785659
Weiqiang Wang, Salvador Ventura
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.
淀粉样蛋白具有高度有序的纤维状结构。其中许多组合似乎与人类疾病有关。然而,淀粉样蛋白原纤维的可控、稳定、可调和鲁棒性可以被利用来构建具有广泛应用于生物医学和生物技术的卓越纳米材料。功能性朊病毒构成一类特殊的淀粉样蛋白。这些可传播的蛋白质呈现模块化结构,无序的朊病毒结构域负责组装,一个或多个球形结构域负责活性。重要的是,原始的球状蛋白可以用任何感兴趣的蛋白代替,而不会损害纤颤电位。这些基因融合形成原纤维,其中球状结构域保持折叠,呈现功能性纳米结构。然而,在某些情况下,空间位阻限制了这些原纤维的活性。这一限制可以通过将朊病毒结构域分解成更短的序列来解决,这些序列既能保持其自组装特性,又能更好地进入纤维状状态的活性蛋白。在这篇综述中,我们将讨论类似朊病毒的功能纳米材料的性质以及这些生物相容性纤维排列的惊人应用。
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引用次数: 4
The cellular prion protein promotes neuronal regeneration after acute nasotoxic injury. 细胞朊蛋白促进急性鼻毒性损伤后神经元再生。
IF 1.9 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1714373
Lindsay E Parrie, Jenna A E Crowell, Julie A Moreno, Stephanie S Suinn, Glenn C Telling, Richard A Bessen

Adult neurogenesis, analogous to early development, is comprised of several, often concomitant, processes including proliferation, differentiation, and formation of synaptic connections. However, due to continual, asynchronous turn-over, newly-born adult olfactory sensory neurons (OSNs) must integrate into existing circuitry. Additionally, OSNs express high levels of cellular prion protein (PrPC), particularly in the axon, which implies a role in this cell type. The cellular prion has been shown to be important for proper adult OSN neurogenesis primarily by stabilizing mature olfactory neurons within this circuitry. However, the role of PrPC on each specific adult neurogenic processes remains to be investigated in detail. To tease out the subtle effects of prion protein expression level, a large population of regenerating neurons must be investigated. The thyroid drug methimazole (MTZ) causes nearly complete OSN loss in rodents and is used as a model of acute olfactory injury, providing a mechanism to induce synchronized OSN regeneration. This study investigated the effect of PrPC on adult neurogenesis after acute nasotoxic injury. Altered PrPC levels affected olfactory sensory epithelial (OSE) regeneration, cell proliferation, and differentiation. Attempts to investigate the role of PrPC level on axon regeneration did not support previous studies, and glomerular targeting did not recover to vehicle-treated levels, even by 20 weeks. Together, these studies demonstrate that the cellular prion protein is critical for regeneration of neurons, whereby increased PrPC levels promote early neurogenesis, and that lack of PrPC delays the regeneration of this tissue after acute injury.

成人神经发生与早期发育类似,由增殖、分化和突触连接形成等几个通常同时发生的过程组成。然而,由于持续的、异步的转换,新生的成年嗅觉感觉神经元(OSNs)必须整合到现有的电路中。此外,osn表达高水平的细胞朊病毒蛋白(PrPC),特别是在轴突,这意味着在这种细胞类型中起作用。细胞朊病毒已被证明是重要的,主要是通过稳定成熟的嗅觉神经元在这个电路中的正常成人OSN神经发生。然而,PrPC在每个特定成人神经源性过程中的作用仍有待详细研究。为了梳理出朊蛋白表达水平的微妙影响,必须对大量再生神经元进行研究。甲状腺药物甲巯咪唑(methimazole, MTZ)导致啮齿动物几乎完全OSN丢失,并作为急性嗅觉损伤模型,提供了一种诱导OSN同步再生的机制。本研究探讨了PrPC对急性鼻毒性损伤后成体神经发生的影响。PrPC水平的改变影响嗅觉感觉上皮(OSE)的再生、细胞增殖和分化。试图研究PrPC水平对轴突再生的作用并不支持先前的研究,肾小球靶向性甚至在20周后也没有恢复到载体处理的水平。总之,这些研究表明,细胞朊蛋白对神经元的再生至关重要,因此,PrPC水平的升高促进了早期神经发生,而PrPC的缺乏会延迟急性损伤后该组织的再生。
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引用次数: 0
Cross-validation of the RT-QuIC assay for the antemortem detection of chronic wasting disease in elk. RT-QuIC法在麋鹿慢性消耗性疾病死前检测中的交叉验证
IF 2.3 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1716657
N J Haley, R Donner, D M Henderson, J Tennant, E A Hoover, M Manca, B Caughey, N Kondru, S Manne, A Kanthasamay, S Hannaoui, S C Chang, S Gilch, S Smiley, G Mitchell, A D Lehmkuhl, B V Thomsen

Chronic wasting disease is a progressively fatal, horizontally transmissible prion disease affecting several members of the cervid species. Conventional diagnosis relies on ELISA or IHC evaluation using tissues collected post-mortem; however, recent research has focused on newly developed amplification techniques using samples collected antemortem. The present study sought to cross-validate the real-time quaking-induced conversion assay (RT-QuIC) evaluation of rectal biopsies collected from an elk herd with endemic CWD, assessing both binary positive/negative test results as well as relative rates of amplification between laboratories. We found that results were correlative in both categories across all laboratories performing RT-QuIC, as well as to conventional IHC performed at a national reference laboratory. A significantly higher number of positive samples were identified using RT-QuIC, with results seemingly unhindered by low follicle counts. These findings support the continued development and implementation of amplification assays in the diagnosis of prion diseases of veterinary importance, targeting not just antemortem sampling strategies, but post-mortem testing approaches as well.

慢性消耗性疾病是一种逐渐致命的水平传播的朊病毒疾病,影响子宫颈物种的一些成员。传统的诊断依赖于ELISA或免疫组化评估,使用死后收集的组织;然而,最近的研究集中在使用生前收集的样本的新开发的扩增技术上。本研究试图交叉验证从患有地方病的麋鹿群收集的直肠活检组织中采集的实时振动诱导转化试验(RT-QuIC)评估,评估二元阳性/阴性检测结果以及实验室之间的相对扩增率。我们发现,在所有进行RT-QuIC的实验室以及在国家参考实验室进行的常规IHC中,这两个类别的结果都是相关的。使用RT-QuIC鉴定出的阳性样本数量显著增加,结果似乎不受低卵泡计数的影响。这些发现支持在诊断具有兽医重要性的朊病毒疾病中继续发展和实施扩增分析,不仅针对死前采样策略,而且针对死后检测方法。
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引用次数: 19
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Prion
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