RT-QuIC is a shaking-based cyclic amplification technique originally developed in the prion field to detect minute amounts of scrapie prion protein (PrPSc). In this study, we applied the RT-QuIC assay to investigate a-synuclein (a-syn) seeding activity in brains of Dementia with Lewy Body (DLB) patients and in brains of G2-3 transgenic mice expressing human a-syn with A53T mutation. The results show

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

We previously discovered three carbazole derivatives, GJP14 (1-piperidinylmethyl-2-(1-oxo-6-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)-ethan-1-ol) with anti-prion activity, GJC29 (benzylamino-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol) with anti-cancer activity, and THC19 (1-piperidinylmethyl-2-(1,2,3,4-tetrahydrocarnazol-9-yl)-ethan-1-ol) with anti-influenza virus activity. During optimization of

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),

ABSTRACT Chronic-wasting disease (CWD) is a prion-derived fatal neurodegenerative disease that has affected wild cervid populations on a global scale. Susceptibility has been linked unambiguously to several amino acid variants within the prion protein gene (PRNP). Quantifying their distribution across landscapes can provide critical information for agencies attempting to adaptively manage CWD. Here

Creutzfeldt-Jakob disease (CJD) is a prion disease, usually presented with memory loss, ataxia, dementia, myoclonus, involuntary movements and psychiatric problems. D178N-homozygous 129M genotype has been recognized in the diagnosis of fatal familial insomnia (FFI) globally. Here we report a patient presented with progressive left upper limb stiffness, bradykinesia, hypomimia and weight loss (10 kg)

Genetic Creutzfeldt-Jakob disease (gCJD) with a mutation in codon 180 of the prion protein gene (V180I gCJD) is the most common form of gCJD in Japan, but only a few cases have been reported in Europe and the United States. It is clinically characterized by occurring in the elderly and presenting as slowly progressive dementia, although it generally shows less cerebellar and pyramidal symptoms than

ABSTRACT Chronic wasting disease (CWD) is caused by prions, infectious proteinaceous particles, PrPCWD. We sequenced the PRNP gene of 2,899 white-tailed deer (WTD) from Illinois and southern Wisconsin, finding 38 haplotypes. Haplotypes A, B, D, E, G and 9 others encoded Q95G96S100N103A123Q226, designated ‘PrP variant A.’ Haplotype C and 4 other haplotypes encoded PrP ‘variant C’ (Q95S96S100N103A123Q226)

(2020). Correction. Prion: Vol. 14, No. 1, pp. 206-206.

ABSTRACT Periodic sharp wave complexes (PSWCs), identified using electroencephalography, are observed in less than half of patients with the methionine homozygosity type 2 cortical (MM2c) form of sporadic Creutzfeldt-Jakob disease (sCJD), and only at a later stage of the disease. In this study, we identified early and specific markers on the electroencephalograms (EEGs) of patients with MM2c-sCJD.

ABSTRACT Prion diseases are characterized by the self-templated misfolding of the cellular prion protein (PrPC) into infectious aggregates (PrPSc). The detailed molecular basis of the misfolding and aggregation of PrPC remains incompletely understood. It is believed that the transient misfolding of PrPC into partially structured intermediates precedes the formation of insoluble protein aggregates and

ABSTRACT PRNP genotypes, number of octarepeats (PHGGGWGQ) and indels in the PRNP promoter can influence the progression of prion disease in mammals. We found no relationship between presence of promoter indels in white-tailed deer and mule deer from Nebraska and CWD presence. White-tailed deer with the 95 H allele and G20D mule deer were more likely to be CWD-free, but unlike other studies white-tailed

ABSTRACT Swallowing function in long-term survivors with Creutzfeldt-Jakob disease (CJD) remains unknown. Herein, we demonstrated serial evaluation of swallowing function in a case with V180I genetic CJD (gCJD) using videofluoroscopic examination of swallowing (VF). A 69-year-old woman was admitted to our hospital because of bradykinesia and memory disturbances 4 months after the onset of symptoms

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

ABSTRACT Fatal Familial Insomnia (FFI) is one of the most popular genetic prion disease (gPrD) in China. Unlike the other types of human prion diseases, FFI patients show distinctive neuropathological characteristics, such as less deposition of PrPSc, low tissue infectivity and severe neuron losses in some special brain regions. Compared with other gPrDs, the positive reactions of cerebrospinal fluid

ABSTRACT A rapid-acting insulin lispro and long-acting insulin glargine are commonly used for the treatment of diabetes. Clinical cases have described the formation of injectable amyloidosis with these insulin analogues, but their amyloid core regions of fibrils were unknown. To reveal these regions, we have analysed the hydrolyzates of insulin fibrils and its analogues using high-performance liquid

ABSTRACT Genetic Creutzfeldt–Jakob disease (gCJD) is characterized by mutations in the PRNP gene and represents approximately 10–15% of the human prion diseases. Here, we report a 42-year-old Chinese man who was diagnosed with gCJD. The patient had a rare mutation in codon 196 (E196A) of PRNP leading to an exchange of amino acid from glutamic acid (E) to alanine (A). The polymorphism of codon 129 in

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, incurable, and fatal neurodegenerative disorder. The objective of this study was to describe the clinical features and survival time of Chinese sCJD patients, and to explore the associations between clinical data and survival. In this study, we analysed the clinical data of 21 sCJD patients in a tertiary care hospital and used all Chinese case material

Creutzfeldt-Jackob disease (CJD), the most common human prion disorder, is frequently accompanied by ageing-associated neurodegenerative conditions, such as Alzheimer's disease and Parkinson's disease. Although cross-seeding of amyloidogenic proteins (APs), including amyloid β and α-synuclein, may be critical in the co-morbidity of neurodegenerative disorders, the direct interaction of APs with prion

The clinical characteristics of genetic Creutzfeldt-Jakob disease (gCJD) with a V180I mutation in the PRNP gene (V180I gCJD) are unique: elderly-onset, gradual progression, sporadic fashion, and cortical oedematous hyper-intensity on diffusion-weighted MRI (DW-MRI). This phenotype may become a potential target of future clinical therapeutic trials. The average disease duration of V180I gCJD patients

Cellular prion protein (PrPC) is a plasma membrane glycophosphatidylinositol-anchored protein and it is involved in multiple functions, including neuroprotection and oxidative stress. So far, most of the PrPC functional research is done in neuronal tissue or cell lines; the role of PrPC in non-neuronal tissues such as liver is only poorly understood. To characterize the role of PrPC in the liver, a

Semi-denaturing detergent agarose gel electrophoresis (SDD-AGE) was proposed by Vitaly V. Kushnirov in the Michael D. Ter-Avanesyan's laboratory as a method to compare sizes of amyloid aggregates. Currently, this method is widely used for amyloid investigation, but mostly as a qualitative approach. In this work, we assessed the possibilities and limitations of the quantitative analysis of amyloid aggregate

(2019). THERPA v2: an update of a small molecule database related to prion protein regulation and prion disease progression. Prion: Vol. 13, No. 1, pp. 197-198.

Recent concern about the possible secondary spread of vCJD through blood transfusion and blood products has highlighted the need for a sensitive test for the identification of PrP(TSE/res) in clinical specimens collected in a non-invasive way. In addition, a more accurate estimate of the prevalence of pre-clinical vCJD in the population may be possible if there were a test that could be applied to

Our laboratory recently reported a novel prion [SWI+], in the budding yeast Saccharomyces cerevisiae. [SWI+] is the prion form of Swi1, a component of the SWI/SNF chromatin-remodeling complex. Cells harboring [SWI+] exhibit a partial loss-of-function phenotype for SWI/SNF, which can be easily assayed by poor growth on some non-fermentable carbon sources such as raffinose.Swi1 is unique among yeast

Infectious amyloid forms of the release factor, Sup35, comprise the yeast prion [PSI+]. This protein-based unit of inheritance is an evolutionary capacitor able to release cryptic genetic variation during environmental stress and generate potentially beneficial phenotypes. Genetic data have uncovered a sophisticated proteostasis network that tightly regulates [PSI+] formation, propagation and elimination

Scrapie and CWD are horizontally transmissible, and the environment likely serves as a stable reservoir of infectious prions, facilitating a sustained incidence of CWD in free-ranging cervid populations and complicating efforts to eliminate disease in captive herds. Prions will enter the environment through mortalities and/or shedding from live hosts. Unfortunately, a sensitive detection method to

RNAs are exported from the nucleus to the cytoplasm, where they undergo translation and produce proteins needed for the cellular life cycle. Some mRNAs are targeted by different RNA decay mechanisms and thereby undergo degradation. The 5'-->3' degradation machinery localizes to cytoplasmic complexes termed P bodies (PBs). They function in RNA turnover, translational repression, RNA-mediated silencing

Insect silks are secreted from diverse gland types; this chapter deals with the silks produced by labial glands of Holometabola (insects with pupa in their life cycle). Labial silk glands are composed of a few tens or hundreds of large polyploid cells that secrete polymerizing proteins which are stored in the gland lumen as a semi-liquid gel. Polymerization is based on weak molecular interactions between

Biomaterials, having evolved over millions of years, often exceed man-made materials in their properties. Spider silk is one outstanding fibrous biomaterial which consists almost entirely of large proteins. Silk fibers have tensile strengths comparable to steel and some silks are nearly as elastic as rubber on a weight to weight basis. In combining these two properties, silks reveal a toughness that

Prions are self-propagating infectious protein aggregates of mammals and fungi. The exact mechanism of prion formation is poorly understood. In a recent study, a comparative analysis of the aggregation propensities of chimeric proteins derived from the yeast Sup35p and mouse PrP prion proteins was performed in neuroblastoma cells. The cytosolic expression of the Sup35p domains NM, PrP and fusion proteins

Early cell biologists perceived centrosomes to be permanent cellular structures. Centrosomes were observed to reproduce once each cycle and to orchestrate assembly a transient mitotic apparatus that segregated chromosomes and a centrosome to each daughter at the completion of cell division. Centrosomes are composed of a pair of centrioles buried in a complex pericentriolar matrix. The bulk of microtubules

A dysfunction in copper homeostasis seems to occur in Alzheimer's disease (AD). We recently demonstrated that an excess of non-ceruloplasmin-copper (i.e., 'free' copper) correlates with the main functional and anatomical deficits as well as the cerebrospinal markers of the disease, thus suggesting that copper contributes to AD neurodegeneration. Aim of this study was to investigate the profile of serum

We previously showed that over production of a fusion protein in which the prion domain of Saccharomyces cerevisiae [PSI(+)] is connected to glutathione S-transferase (GST-Sup35NM) causes a marked decrease in the colony forming ability of Escherichia coli strain BL21 after reaching stationary phase. Evidence indicated that the observed toxicity was attributable to intracellular formation of fibrous

Concerns over the potential for infectious prion proteins to contaminate human biologics and biotherapeutics have been raised from time to time. Transmission of the pathogenic form of prion protein (PrP(Sc)) through veterinary vaccines has been observed, yet no human case through the use of vaccine products has been reported. However, iatrogenic transmissions of PrP(Sc) in humans through blood components

Nucleic acid sequences of the prion gene (PRNP) were examined and genotypes compiled for 76 white-tailed deer from northern Illinois, which previously tested positive for chronic wasting disease (CWD), and 120 negative animals selected to control for geographic location and age. Nine nucleotide polymorphisms, seven silent and two coding, were found in the sampled population. All observed polymorphisms

This review will first recall the phenomena of "cortical inheritance" observed and genetically demonstrated in Paramecium 40 years ago, and later in other ciliates (Tetrahymena, Oxytricha, Paraurostyla), and will analyze the deduced concept of "cytotaxis" or "structural memory." The significance of these phenomena, all related (but not strictly restricted) to the properties of ciliary basal bodies

Amyloid refers to the abnormal fibrous, extracellular, proteinaceous deposits found in organs and tissues. Amyloid is insoluble and is structurally dominated by beta-sheet structure. Unlike other fibrous proteins it does not commonly have a structural, supportive or motility role but is associated with the pathology seen in a range of diseases known as the amyloidoses. These diseases include Alzheimer's

The structure and the dissociation reaction of oligomers Pr(Poligo) from reduced human prion huPrP(C)(23-231) have been studied by (1)H-NMR and tryptophan fluorescence spectroscopy at varying pressure, along with circular dichroism and atomic force microscopy. The 1H-NMR and fluorescence spectral feature of the oligomer is consistent with the notion that the N-terminal residues including all seven

Prion protein (PrP)-like molecule, doppel (Dpl), is neurotoxic in mice, causing Purkinje cell degeneration. In contrast, PrP antagonizes Dpl in trans, rescuing mice from Purkinje cell death. We have previously shown that PrP with deletion of the N-terminal residues 23-88 failed to neutralize Dpl in mice, indicating that the N-terminal region, particularly that including residues 23-88, may have trans-protective

A case of L-type-like atypical bovine spongiform encephalopathy was detected in 14-year-old Japanese black beef cattle (BSE/JP24). To clarify the biological and biochemical properties of the prion in BSE/JP24, we performed a transmission study with wild-type mice and bovinized transgenic mice (TgBoPrP). The BSE/JP24 prion was transmitted to TgBoPrP mice with the incubation period of 199.7 +/- 3.4 days

Insulin-degrading enzyme (IDE) is a conserved Zn(2+)metalloendopeptidase involved in insulin degradation and in the maintenance of brain steady-state levels of amyloid beta peptide (Abeta) of Alzheimer's disease (AD). Our recent demonstration that IDE and Abeta are capable of forming a stoichiometric and extremely stable complex raises several intriguing possibilities regarding the role of this unique

The uncontrolled formation of amyloid fibers is the hallmark of more than twenty human diseases. In contrast to disease-associated amyloids, which are the products of protein misfolding, E. coli assembles functional amyloid fibers called curli on its surface using an elegant biogenesis machine. Composed of a major subunit, CsgA, and a minor subunit, CsgB, curli play important roles in host cell adhesion

The study of fungal prion proteins affords remarkable opportunities to elucidate both intragenic and extragenic effectors of prion propagation. The yeast prion protein Sup35 and the self-perpetuating [PSI+] prion state is one of the best characterized fungal prions. While there is little sequence homology among known prion proteins, one region of striking similarity exists between Sup35p and the mammalian

Co-inoculation of prion strains into the same host can result in interference, where replication of one strain hinders the ability of another strain to cause disease. The drowsy (DY) strain of hamster-adapted transmissible mink encephalopathy (TME) extends the incubation period or completely blocks the hyper (HY) strain of TME following intracerebral, intraperitoneal or sciatic nerve routes of inoculation

In order to obtain RNA aptamers against bovine prion protein (bPrP), we carried out in vitro selection from RNA pools containing a 55-nucleotide randomized region to target recombinant bPrP. Most of obtained aptamers contained conserved GGA tandem repeats (GGA)(4) and aptamer #1 (apt #1) showed a high affinity for both bPrP and its beta isoform (bPrP-beta). The sequence of apt #1 suggested that it

We propose models for in vitro grown mammalian prion protein fibrils based upon left handed beta helices formed both from the N-terminal and C-terminal regions of the proteinase resistant infectious prion core. The C-terminal threading onto a beta-helical structure is almost uniquely determined by fixing the cysteine disulfide bond on a helix corner. In comparison to known left handed helical peptides

Glucantransferase Bgl2p is a major conserved cell wall constituent described for a wide range of yeast species. In the baker's yeast Saccharomyces cerevisiae it is the only non-covalently bound cell wall protein that cannot be released from cell walls by sequential SDS and trypsin treatment. It contains seven amyloidogenic determinants. Circular dichroism analysis and fluorescence spectroscopy with

Cellular prion protein (PrP(C)) appears to be involved in numerous physiological processes. We have recently shown a novel modulation of NMDA receptors by PrP(C) that results in neuroprotection via silencing of NMDA receptors containing NR2D subunits, whereas no effects on AMPA receptor function could be observed (Khosravani, et al. J Cell Biol 2008; 181:551). Here we show that PrP-null mice show a

In the past decade, the interaction between prions and nucleic acids has garnered significant attention from the scientific community. for many years, the participation of RNA and/or DNA in prion pathology has been largely ruled out by the "protein-only" hypothesis, but this is now being reconsidered. Experimental data now indicate that nucleic acids (particularly RNA), besides being carriers of genetic

The prion infection is a conversion of host encoded prion protein (PrP) from its cellular isoform PrP(C) into the pathological and infectious isoform PrP(Sc); the conversion process was investigated by in vitro studies using recombinant and cellular PrP and natural PrP(Sc). We present a brief summary of the results determined with our in vitro conversion system and the derived mechanistic models. We

Proteins are a major constituent of cells with specific biological functions. Besides the primary structure that is simply the sequence of amino acids that comprise a protein, the secondary structure represents the first step of folding defining its general conformation. The biological functions of proteins are directly dependent on the acquisition of their conformation. The same protein can have different

In vivo amyloid formation is a widespread phenomenon in eukaryotes. Self-perpetuating amyloids provide a basis for the infectious or heritable protein isoforms (prions). At least for some proteins, amyloid-forming potential is conserved in evolution despite divergence of the amino acid (aa) sequences. In some cases, prion formation certainly represents a pathological process leading to a disease. However

The pathogenic mechanism(s) underlying neurodegenerative diseases associated with protein misfolding is unclear. Several studies have implicated ER stress pathways in neurodegenerative conditions, including prion disease, amyotrophic lateral sclerosis, Alzheimer's disease and many others. The ER stress response and upregulation of ER stress-responsive chaperones is observed in the brains of patients

Exposure to high temperature or other stresses induces a synthesis of heat shock proteins. Many of these proteins are molecular chaperones, and some of them help cells to cope with heat-induced denaturation and aggregation of other proteins. In the last decade, chaperones have received increased attention in connection with their role in maintenance and propagation of the Saccharomyces cerevisiae prions

Prion protein (PrP), the causative agent of transmissible spongiform encephalopathies, is synthesized in the endoplasmic reticulum (ER) where it undergoes numerous covalent modifications. Here we investigate the interdependence and regulation of PrP oxidative folding, N-glycosylation and GPI addition in diverse ER conditions. Our results show that formation of the single disulphide bond is a pivotal

Prion disease is a neurodegenerative disorder, in which the normal prion protein (PrP) changes structurally into an abnormal form and accumulates in the brain. There is a great demand for the development of a viable approach to diagnosis and therapy. Not only has the ligand against PrP been used for diagnosis, but it has also become a promising tool for therapy, as an antibody. Aptamers are a novel

Yeast prion determinants are related to polymerization of some proteins into amyloid-like fibers. The [PSI(+)] determinant reflects polymerization of the Sup35 protein. Fragmentation of prion polymers by the Hsp104 chaperone represents a key step of the prion replication cycle. The frequency of fragmentation varies depending on the structure of the prion polymers and defines variation in the prion

We identified the 37kDa/67kDa laminin receptor (LRP/LR) as a cell surface receptor for the cellular prion protein (PrP(c)) and the infectious prion protein (PrP(Sc)). Recently, we showed that anti-LRP/LR antibody W3 cured scrapie infected N2a cells. Here, we demonstrate that W3 delivered by passive immunotransfer into C57BL/6 mice reduced the PrP(Sc) content in the spleen significantly by 66%, demonstrating