*  The origin of the prion agent of kuru: molecular and biological strain typing | Philosophical Transactions of the Royal Society...
Human prion diseases are fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia, kuru and variant CJD (vCJD; Collinge 2001, 2005; Wadsworth & Collinge 2007). Their central feature is the post-translational conversion of host-encoded, cellular prion protein (PrPC) to an abnormal isoform, designated PrPSc (Prusiner 1982; Collinge 2001). Substantial evidence indicates that an abnormal PrP isoform is the principal, if not the sole, component of the transmissible infectious agent, or prion (Prusiner 1982; Collinge 2001; Weissmann 2004; Collinge & Clarke 2007). Human prion diseases are biologically unique in that the disease process can be triggered through inherited germ line mutations in the human prion protein gene (PRNP), infection (by inoculation, or in some cases by dietary exposure) with prion-infected tissue or by rare sporadic events that generate PrPSc (Collinge 2001, 2005; Wadsworth et al. 2003; ...
  http://rstb.royalsocietypublishing.org/content/363/1510/3747
*  What Is Prion Disease?
Between 10 and 15 percent of all cases of prion disease are caused by mutations in the PRNP gene. Because they can run in families, these forms of prion disease are classified as familial. Familial prion diseases, which have overlapping signs and symptoms, include familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI).. The PRNP gene provides instructions for making a protein called prion protein (PrP). Although the precise function of this protein is unknown, researchers have proposed roles in several important processes.. These include the transport of copper into cells, protection of brain cells (neurons) from injury (neuroprotection), and communication between neurons. In familial forms of prion disease, PRNP gene mutations result in the production of an abnormally shaped protein, known as PrPSc, from one copy of the gene.. In a process that is not fully understood, PrPSc can attach (bind) to the normal protein (PrPC) and ...
  https://reliawire.com/prion-disease/
*  PLOS Pathogens: Genesis of Mammalian Prions: From Non-infectious Amyloid Fibrils to a Transmissible Prion Disease
Author Summary The transmissible agent of prion disease consists of a prion protein in its abnormal conformation (PrPSc), which replicates itself according to the template-assisted mechanism. This mechanism postulates that the folding pattern of a newly recruited polypeptide chain accurately reproduces that of a PrPSc. The current study reports that infectious prions and transmissible prion disease can be triggered in wild type animals by amyloid fibrils produced from recombinant prion prtotein, which are structurally different from PrPSc and lacks any detectable PrPSc particles. This work introduces a new hypothesis that transmissible prion diseases can be induced by prion protein structures different from that of authentic PrPSc and suggests that a new mechanism for triggering PrPSc formation different from the classical templating exists. The current work provides important new insight into the mechanisms underlying genesis and evolution of the transmissible states of the prion protein ...
  http://journals.plos.org/plospathogens/article/comments?id=10.1371/journal.ppat.1002419&imageURI=info:doi/10.1371/journal.ppat.1002419.g005
*  Viruses | Free Full-Text | Cellular Aspects of Prion Replication In Vitro
Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders in mammals that are caused by unconventional agents predominantly composed of aggregated misfolded prion protein (PrP). Prions self-propagate by recruitment of host-encoded PrP into highly ordered b-sheet rich aggregates. Prion strains differ in their clinical, pathological and biochemical characteristics and are likely to be the consequence of distinct abnormal prion protein conformers that stably replicate their alternate states in the host cell. Understanding prion cell biology is fundamental for identifying potential drug targets for disease intervention. The development of permissive cell culture models has greatly enhanced our knowledge on entry, propagation and dissemination of TSE agents. However, despite extensive research, the precise mechanism of prion infection and potential strain effects remain enigmatic. This review summarizes our current knowledge of the cell biology and ...
  http://www.mdpi.com/1999-4915/5/1/374
*  Viruses | Free Full-Text | Cellular Aspects of Prion Replication In Vitro | Notes
Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders in mammals that are caused by unconventional agents predominantly composed of aggregated misfolded prion protein (PrP). Prions self-propagate by recruitment of host-encoded PrP into highly ordered b-sheet rich aggregates. Prion strains differ in their clinical, pathological and biochemical characteristics and are likely to be the consequence of distinct abnormal prion protein conformers that stably replicate their alternate states in the host cell. Understanding prion cell biology is fundamental for identifying potential drug targets for disease intervention. The development of permissive cell culture models has greatly enhanced our knowledge on entry, propagation and dissemination of TSE agents. However, despite extensive research, the precise mechanism of prion infection and potential strain effects remain enigmatic. This review summarizes our current knowledge of the cell biology and ...
  http://www.mdpi.com/1999-4915/5/1/374/notes
*  ASSESSING CEREBELLAR FUNCTION IN PRION DISEASE | Journal of Neurology, Neurosurgery & Psychiatry
Ataxia is common in various forms of human prion diseases but there is a dearth of validated assessment tools and data on the subject. Originally used for inherited cerebellar ataxias, the Scale for Assessment and Rating of cerebellar Ataxia (SARA) and Composite Cerebellar Functional Severity Score (CCFS) have been incorporated into the National Prion Monitoring Cohort (NPMC) as semi-quantitative measures of posture, gait, kinetic dysfunction and speech in patients with sporadic and inherited Creutzfeldt-Jakob disease (CJD).. SARA and CCFS assessments were completed for patients with sporadic CJD (sCJD, n=119), and inherited prion disease (IPD, n=46). Patients were concurrently scored on the Medical Research Council Prion Disease Rating Scale (MRC PDRS), a functionally-oriented measure of disease progression validated in CJD patients.. SARA scores in sCJD and IPD patients showed a strong, statistically significant correlation with the MRC PDRS. The SARA score may be useful in providing ...
  http://jnnp.bmj.com/content/87/12/e1.138
*  BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA: September 2012
Prion diseases are transmissible neurodegenerative disorders affecting both humans and animals. The cellular prion protein, ... He said while Alzheimer's and Parkinson's were not transmissible like prion diseases such as vCJD, they similarly released the ... modulates the function of miRISC on the MVB and subsequent release of miRNA in exosomes during prion diseases certainly ... proteins are stained using antibodies that can identify a specific banding pattern associated with prion diseases including BSE ...
  http://madcowtesting.blogspot.com/2012_09_01_archive.html
*  Eldorado: Role of PrPc Related to Apoptosis
Prion diseases are transmissible neurodegenerative disorders that are invariably fatal in human and animals. Although the nature of the infectious agent and pathogenic mechanisms of prion diseases are not clear, it has been reported to be associated with aberrant metabolism of cellular prion protein (PrPc). In various reports, it has been postulated that PrPc may be involved in programmed cell death or apoptosis. Apoptosis of neuronal cells can also be induced in vitro by exposure to PrPsc or a neurotoxic peptide fragment corresponding to amino acids 106-126,118-135 of human prion protein (PrP106-126;PrP118-135). While the anti-apoptotic and anti-oxidative function of PrPc is regulated by not only OR (Octapeptide Region,amino acid residue 51-91) but also the N-terminal half of HR(Hydrophobic Region, amino acids residue 95-132). PrPc may participate in apoptosis through extrinsic pathway by binding to certain chaperon molecules or through induced by certain stresses like inflammatory factors. It ...
  https://eldorado.tu-dortmund.de/handle/2003/25671
*  Activation of the unfolded protein response and granulovacuolar degeneration are not common features of human prion pathology |...
Many neurodegenerative diseases are characterized by the deposition of misfolded protein aggregates. Therefore, it is suggested that these diseases share the involvement of similar cellular signalling mechanisms associated with protein folding and clearance. Previously, we have demonstrated increased presence of several UPR activation markers, including pPERK and pIRE1α, in post-mortem brain tissue of AD, FTLD-tau and PD [24, 40, 41]. In the present study, we aimed to further elucidate the involvement of the UPR in human prion pathology. To this end, we selected cases from the Dutch cohort of human prion disease patients [29] and performed immunohistochemistry to visualize UPR activation markers on post-mortem frontal cortex sections. Immunoreactivity for pIRE1α and pPERK was not increased in human prion disease cases compared to non-neurological controls. In addition, immunoreactivity for CK1δ, a marker associated with GVD and cellular stress, was not elevated in human prion disease ...
  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-016-0383-7
*  Prion Diseases video: Prion Disease
This documentary deals with a very rare and unusual prion disease called Fatal Familial Insomnia or FFI for short. FFI is a prion disease that targets the thalamus, of which of its many functions ...
  http://prion-diseases.purzuit.com/video/VxRXZWqAvUw.html
*  Young onset dementia | Postgraduate Medical Journal
The prion diseases are transmissible neurodegenerations characterised pathologically by diffuse brain spongiosis and deposition of an abnormal fibrillar prion glycoprotein, PrP, which is encoded by the PRNP gene on chromosome 20.34 Different PrP conformations and glycosylation patterns give rise to various strains, which show species specificity. The paradigm for these disorders is scrapie, a disease of sheep and goats, for which analogues exist in a number of other species. Human prion diseases, occur in sporadic (approximately 90% of cases), acquired (generally iatrogenic), and inherited forms. Creutzfeldt-Jakob disease (CJD) is the most common, with an approximate incidence of one case per million worldwide. Kuru, described in the Fore linguistic group of New Guinea highlanders, was transmitted by ritual cannibalism; the disease has largely disappeared since this practice was abolished in the 1950s, although occasional new cases may occur, suggesting a very long presymptomatic phase. The ...
  http://pmj.bmj.com/content/80/941/125
*  Abnormal Brain Iron Homeostasis in Human and Animal Prion Disorders
Author Summary Prion disorders are neurodegenerative conditions of humans and animals that are invariably fatal. The main agent responsible for neurotoxicity in all prion disorders is PrP-scrapie (PrPSc), a β-sheet rich isoform of a normal cell-surface glycoprotein, the prion protein (PrPC). Deposits of PrPSc in the brain parenchyma are believed to induce neurotoxicity, though the underlying mechanisms are not entirely clear. Emerging evidence from prion-infected cell and mouse models implicates redox-iron in prion disease-associated neurotoxicity. However, a systematic evaluation of iron homeostasis in prion disease-affected brains and the underlying mechanism of iron dyshomeostasis are lacking. In this report, we demonstrate that prion disease-affected human, mouse, and hamster brains exhibit a state of iron deficiency in the presence of excess total brain iron, resulting in a state of iron imbalance. The underlying cause of this phenotype is likely sequestration of iron in cellular ferritin that
  http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000336
*  Protein Folding Activity of the Ribosome (PFAR) : A Target for Antiprion Compounds
Prion diseases are fatal neurodegenerative diseases affecting mammals. Prions are misfolded amyloid aggregates of the prion protein (PrP), which form when the alpha helical, soluble form of PrP converts to an aggregation-prone, beta sheet form. Thus, prions originate as protein folding problems. The discovery of yeast prion(s) and the development of a red-/white-colony based assay facilitated safe and high-throughput screening of antiprion compounds. With this assay three antiprion compounds; 6-aminophenanthridine (6AP), guanabenz acetate (GA), and imiquimod (IQ) have been identified. Biochemical and genetic studies reveal that these compounds target ribosomal RNA (rRNA) and inhibit specifically the protein folding activity of the ribosome (PFAR). The domain V of the 23S/25S/28S rRNA of the large ribosomal subunit constitutes the active site for PFAR. 6AP and GA inhibit PFAR by competition with the protein substrates for the common binding sites on the domain V rRNA. PFAR ...
  http://uu.diva-portal.org/smash/record.jsf?pid=diva2:775067
*  British Library EThOS: Cell death in prion disease
Prion diseases are a group of fatal neurodegenerative diseases, including CJD and scrapie, which are thought to be caused by a protein termed a prion (PrP). As manganese has previously been suggested to be involved in prion disease we have investigated manganese binding to PrP and its role in the toxicity of the protein. We have shown that manganese bound PrP (MnPrP) has several of the characteristics of the disease form of PrP, including protease resistance and toxicity that is dependent on cellular PrP expression. Further investigation into the mechanism of toxicity revealed that MnPrP is significantly more toxic to neuronal cells than nonmanganese bound PrP and that toxicity requires the presence of known metal binding residues within the protein. We have demonstrated that treatment of neuronal cells with MnPrP causes caspase 3 activation and apoptosis, as demonstrated by DNA laddering, and we hypothesise that caspase 3 is activated by a p38 pathway. Treatment of neurones with MnPrP also ...
  http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.488879
*  James Lab
Prion diseases are fatal neurodegenerative conditions. Probably the most famous at the moment is bovine spongiform encephalopathy (BSE) or 'mad cow' disease, with substantial evidence that bovine prions from infected cows have been transmitted to humans, manifesting a new variant of Creutzfeldt-Jakob disease. Much data indicate that a protein commonly found in neuronal cells, the prion protein PrP, undergoes a structural change from its common cellular form (PrP-C) to an abnormal form (PrP-Sc) that may be responsible for the propagation of fatal neurodegenerative diseases. Indeed, it appears that PrP-Sc induces PrP-C molecules to convert. A few years ago, we used NMR to determine the structure of a 142-residue recombinant protein (residues 90-231 from the full-length 23-231 sequence of PrP) corresponding to the normal cellular form of the protein. This work was carried out in collaboration with Prof. Stan Prusiner's lab. Structure stability and dynamics are almost certainly essential for ...
  http://picasso.ucsf.edu/prion.html
*  Prion Diseases | NIH: National Institute of Allergy and Infectious Diseases
Much about TSE diseases remains unknown. The diseases are characterized by certain misshapen protein molecules that appear in brain tissue. Normal forms of these prion protein molecules reside on the surface of many types of cells, including brain cells, but scientists do not understand what normal prion protein does. On the other hand, scientists believe that abnormal prion protein, which clumps together and accumulates in brain tissue, is the likely cause of the brain damage that occurs in TSE diseases. Scientists do not have a good understanding of what causes the normal prion protein to take on the misshapen abnormal form.. ...
  https://www.niaid.nih.gov/diseases-conditions/prion-diseases
*  Prion disease treatable if caught early ( Studies in mice have indicated that the...)
Studies in mice have indicated that the effects of prion disease could...The researchers Giovanna Mallucci and colleagues reported their find...Prion disease-such as the version of Creutzfeldt-Jakob disease believe...However in previous studies with prion-infected mice Mallucci and co...In the new studies published in Neuron they established that cognitiv...,Prion,disease,treatable,if,caught,early,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
  http://www.bio-medicine.org/biology-news/Prion-disease-treatable-if-caught-early-4439-1/
*  Adenosine Transporters
Prion diseases or transmissible spongiform encephalopathies are a rare group of fatal neurodegenerative illnesses in humans and animals caused by misfolding of prion protein (PrP). was Rabbit Polyclonal to MED8. monitored by proteinase K-digestion assay. Our results indicate that S230C-GPI in the liberation of lipid vesicles has high tendency to misfold into amyloid fibrils while the membrane-bound S230C-GPI proteins are highly stable and rarely convert into amyloid forms. In addition the role of cholesterol in S230C-GPI was studied. The effect of GPI cholesterol and phospholipid vesicles on misfolding of PrP is usually further discussed. is the Stern-Volmer quenching constant and [BL21 star? (DE3 Life Technologies Grand Island NY USA) cells respectively in 50 mL LB medium overnight. In large-scale culture cells were transferred to TB medium and grew until optical density at 600 nm reached 0.6. Subsequent addition of 1 1 mM isopropyl β-d-1-thiogalactopyranoside induced expression of ...
  http://www.buyresearchchemicalss.net/category/adenosine-transporters/
*  BSE Info - Prions
Prions (the name is derived from proteinacious infectious particle) is the name used by many scientists to describe the pathogen that causes transmissible spongiform encephalopathies (TSE) which are neurodegenerative diseases in mammals. Prions are a disease-causing form of a normal protein called cellular prion protein (PrPC) that is located primarily on the surface of central nervous system cells but also in other tissues of the body in mammals. The specific function of the normal prion protein (PrPC) is not clearly understood, but in experimental models it appears to play a role in protecting cells and helping them respond to oxygen deficiency.1 Prions are extremely small, smaller than viruses, and even through an electron microscope only aggregations (clusters), not individual prions, can be seen.. Prions are unique pathogens in that they appear to have no nucleic acid and thereby differ from viruses, bacteria, fungi and ...
  http://bseinfo.org/Prions.aspx
*  IJMS | Free Full-Text | Role of Prion Protein Aggregation in Neurotoxicity | HTML
In several neurodegenerative diseases, such as Parkinson, Alzheimer's, Huntington, and prion diseases, the deposition of aggregated misfolded proteins is believed to be responsible for the neurotoxicity that characterizes these diseases. Prion protein (PrP), the protein responsible of prion diseases, has been deeply studied for the peculiar feature of its misfolded oligomers that are able to propagate within affected brains, inducing the conversion of the natively folded PrP into the pathological conformation. In this review, we summarize the available experimental evidence concerning the relationship between aggregation status of misfolded PrP and neuronal death in the course of prion diseases. In particular, we describe the main findings resulting from the use of different synthetic (mainly PrP106-126) and recombinant PrP-derived peptides, as far as mechanisms of aggregation and amyloid formation, and how these different spatial conformations can affect neuronal death. In particular, most ...
  http://www.mdpi.com/1422-0067/13/7/8648/htm
*  BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA: June 2013
MOLECULAR BASIS OF HUMAN PRION DISEASES Molecular strain typing Molecular strain typing in the form of classifying the mobility and glycoform ratio of protease-resistant prion protein byWestern blotting is a remarkably useful adjunct to neuropathological assessment during the post-mortem diagnosis of human prion diseases (Fig. 1). The glycoform ratio difference between vCJD and all forms of sCJD is a remarkably robust phenomenon, although the mechanism underlying it remains obscure. All cases of vCJD examined show type 2B PrPres, irrespective of brain region assayed and the PrPres type is also found in lymphoreticular tissues, albeit with presumably tissue-specific minor modification of mobility and an accentuation of the glycoform ratio. Similarly sCJD cases are characterized by a narrow range of glycoform ratios, distinct from vCJD, and the presence of either type 1 or type 2 PrPres (type 1A and type 2A).The PrPres types found in the brain in iCJD and kuru resemble those found in sCJD (type 1A ...
  http://madcowtesting.blogspot.com/2013/06/
*  Thinking Mole's Blog: East African Mystery Disease: Nodding Syndrome
However, I also wonder if this might be a new manifestation of a prion disease, a type of disease (like "mad cow disease") that affects the nervous system and which can be incredibly hard to identify the causative agent. It is not clear to me if the brain pathologies have been tested for prions but it seems like it would be something that could be at least quickly ruled out. To me it sounds like it has some aspects in common, but this could easily be a superficial resemblance. I have seen prions brought up as a possible causative agent but I have seen no data related to this hypothesis. However, one aspect does not fit: most prion diseases are caused by people eating meat from an animal that had a prion disease. Since the prion protein is from another species, the change in the human nervous system is slower to develop and usually only manifests in old age. The fact that this mostly affects children suggests either that it is not a prion disease or that the source is from an ...
  http://healthymole.blogspot.com/2012/03/east-african-mystery-disease-nodding.html
*  Thinking Mole's Blog: March 2012
However, I also wonder if this might be a new manifestation of a prion disease, a type of disease (like "mad cow disease") that affects the nervous system and which can be incredibly hard to identify the causative agent. It is not clear to me if the brain pathologies have been tested for prions but it seems like it would be something that could be at least quickly ruled out. To me it sounds like it has some aspects in common, but this could easily be a superficial resemblance. I have seen prions brought up as a possible causative agent but I have seen no data related to this hypothesis. However, one aspect does not fit: most prion diseases are caused by people eating meat from an animal that had a prion disease. Since the prion protein is from another species, the change in the human nervous system is slower to develop and usually only manifests in old age. The fact that this mostly affects children suggests either that it is not a prion disease or that the source is from an ...
  http://healthymole.blogspot.com/2012_03_01_archive.html
*  Therapeutic approaches for prion and Alzheimer's diseases - Wisniewski - 2007 - The FEBS Journal - Wiley Online Library
Alzheimer's and prion diseases belong to a category of conformational neurodegenerative disorders [Prusiner SB (2001) N Eng J Med344, 1516-1526; Sadowski M & Wisniewski T (2007) Curr Pharm Des 13, 1943-1954; Beekes M (2007) FEBS J 274, 575]. Treatments capable of arresting or at least effectively modifying the course of disease do not yet exist for either one of these diseases. Alzheimer's disease is the major cause of dementia in the elderly and has become an ever greater problem with the aging of Western societies. Unlike Alzheimer's disease, prion diseases are relatively rare. Each year only approximately 300 people in the USA and approximately 100 people in the UK succumb to various forms of prion diseases [Beekes M (2007) FEBS J 274, 575; Sigurdsson EM & Wisniewski T (2005) Exp Rev Vaccines 4, 607-610]. Nevertheless, these disorders have received great scientific and public interest due to the fact that they can be transmissible among humans and in certain conditions from animals to humans. ...
  http://onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2007.05919.x/abstract
*  Snord 3A: A Molecular Marker and Modulator of Prion Disease Progression
Since preventive treatments for prion disease require early identification of subjects at risk, we searched for surrogate peripheral markers characterizing the asymptomatic phases of such conditions. To this effect, we subjected blood mRNA from E200K PrP CJD patients and corresponding family members to global arrays and found that the expression of Snord3A, a non-coding RNA transcript, was elevated several times in CJD patients as compared to controls, while asymptomatic carriers presented intermediate Snord3A levels. In the brains of TgMHu2ME199K mice, a mouse model mimicking for E200K CJD, Snord 3A levels were elevated in an age and disease severity dependent manner, as was the case for brains of these mice in which disease was exacerbated by copper administration. Snord3A expression was also elevated in scrapie infected mice, but not in PrP0/0 mice, indicating that while the expression levels of this transcript may reflect diverse prion etiologies, they are not related to the loss of PrPC's function.
  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0054433