prion proteins


Summary: Membrane glycosylphosphatidylinositol-anchored glycoproteins that may aggregate into rod-like structures. The prion protein (PRNP) gene is characterized by five TANDEM REPEAT SEQUENCES that encode a highly unstable protein region of five octapeptide repeats. Mutations in the repeat region and elsewhere in this gene are associated with CREUTZFELDT-JAKOB DISEASE; FATAL FAMILIAL INSOMNIA; GERSTMANN-STRAUSSLER DISEASE; Huntington disease-like 1, and KURU.

Top Publications

  1. Mastrianni J, Nixon R, Layzer R, Telling G, Han D, DeArmond S, et al. Prion protein conformation in a patient with sporadic fatal insomnia. N Engl J Med. 1999;340:1630-8 pubmed
  2. Teruya K, Oguma A, Nishizawa K, Kamitakahara H, Doh ura K. Pyrene conjugation and spectroscopic analysis of hydroxypropyl methylcellulose compounds successfully demonstrated a local dielectric difference associated with in vivo anti-prion activity. PLoS ONE. 2017;12:e0185357 pubmed publisher
  3. Provenzano L, Ryan Y, Hilton D, Lyons Rimmer J, Dave F, Maze E, et al. Cellular prion protein (PrPC) in the development of Merlin-deficient tumours. Oncogene. 2017;36:6132-6142 pubmed publisher
    ..We suggest that PrPC and its interactor, LR/37/67 kDa, could be potential therapeutic targets for schwannomas and other Merlin-deficient tumours. ..
  4. Honda H, Sasaki K, Takashima H, Mori D, Koyama S, Suzuki S, et al. Different Complicated Brain Pathologies in Monozygotic Twins With Gerstmann-Sträussler-Scheinker Disease. J Neuropathol Exp Neurol. 2017;76:854-863 pubmed publisher
    ..The degree of GSS pathology was mainly related to disease duration. The amyloid plaque formations could be decorated by concomitant neuropathological changes such as ?-synucleinopathy and tauopathy. ..
  5. Lattanzio F, Abu Rumeileh S, Franceschini A, Kai H, Amore G, Poggiolini I, et al. Prion-specific and surrogate CSF biomarkers in Creutzfeldt-Jakob disease: diagnostic accuracy in relation to molecular subtypes and analysis of neuropathological correlates of p-tau and Aβ42 levels. Acta Neuropathol. 2017;133:559-578 pubmed publisher
  6. Konold T, Phelan L, Donnachie B, Chaplin M, Cawthraw S, Gonzalez L. Codon 141 polymorphisms of the ovine prion protein gene affect the phenotype of classical scrapie transmitted from goats to sheep. BMC Vet Res. 2017;13:122 pubmed publisher
    ..Differences in the truncation of disease-associated prion protein between LL141 sheep and those carrying the F141 allele may be responsible for these observations. ..
  7. Huor A, Douet J, Lacroux C, Lugan S, Tillier C, Aron N, et al. Infectivity in bone marrow from sporadic CJD patients. J Pathol. 2017;243:273-278 pubmed publisher
    ..Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. ..
  8. Stincardini C, Massignan T, Biggi S, Elezgarai S, Sangiovanni V, Vanni I, et al. An antipsychotic drug exerts anti-prion effects by altering the localization of the cellular prion protein. PLoS ONE. 2017;12:e0182589 pubmed publisher
    ..Collectively, our results redefine the mechanism by which CPZ exerts anti-prion effects, and support a primary role for dynamins in the membrane recycling of PrPC, as well as in the propagation of infectious prions. ..
  9. Makin S. Pathology: The prion principle. Nature. 2016;538:S13-S16 pubmed publisher

More Information


  1. Shi L, Chen H, Zhang S, Chu T, Zhao Y, Chen Y, et al. Semi-synthesis of murine prion protein by native chemical ligation and chemical activation for preparation of polypeptide-?-thioester. J Pept Sci. 2017;23:438-444 pubmed publisher
    ..This strategy will allow more straightforward access to homogeneously modified PrP variants. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. ..
  2. Zhang D, Qi Y, Klyubin I, Ondrejcak T, Sarell C, Cuello A, et al. Targeting glutamatergic and cellular prion protein mechanisms of amyloid β-mediated persistent synaptic plasticity disruption: Longitudinal studies. Neuropharmacology. 2017;121:231-246 pubmed publisher
    ..Overall, the present findings support the ongoing development of therapeutics for early Alzheimer's disease based on these complementary approaches. ..
  3. Hafner Bratkovic I. Prions, prionoid complexes and amyloids: the bad, the good and something in between. Swiss Med Wkly. 2017;147:w14424 pubmed publisher
    ..Prionoid complexes play important roles far beyond prion diseases and neurodegeneration. ..
  4. Niżyński B, Dzwolak W, Nieznanski K. Amyloidogenesis of Tau protein. Protein Sci. 2017;26:2126-2150 pubmed publisher
    ..Here, we review the current literature on Tau aggregation and discuss mechanisms of propagation of Tau amyloid in the light of the prion-like paradigm. ..
  5. Papasavva Stylianou P, Simmons M, Ortiz Pelaez A, Windl O, Spiropoulos J, Georgiadou S. Effect of Polymorphisms at Codon 146 of the Goat PRNP Gene on Susceptibility to Challenge with Classical Scrapie by Different Routes. J Virol. 2017;91: pubmed publisher
    ..This study provides an experimental transmission model for assessing the genetic susceptibility of goats to scrapie. ..
  6. Zanyatkin I, Stroylova Y, Tishina S, Stroylov V, Melnikova A, Haertle T, et al. Inhibition of Prion Propagation by 3,4-Dimethoxycinnamic Acid. Phytother Res. 2017;31:1046-1055 pubmed publisher
    ..We suggest that DMCA is a perspective dietary compound for prophylaxis of neurodegenerative diseases that needs further research. Copyright © 2017 John Wiley & Sons, Ltd. ..
  7. Alred E, Nguyen M, Martin M, Hansmann U. Molecular dynamics simulations of early steps in RNA-mediated conversion of prions. Protein Sci. 2017;26:1524-1534 pubmed publisher
    ..Changes in stability and secondary structure of the prions upon binding to polyadenosine RNA are evaluated by comparing molecular dynamics simulations of these complexes with that of the unbound prions. ..
  8. Onodera T. Dual role of cellular prion protein in normal host and Alzheimer's disease. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93:155-173 pubmed publisher
    ..Further search for PrPC-interaction molecules using Prnp-/- mice and various types of Prnp-/- cell lines under various conditions may elucidate other important PrPC important functions. ..
  9. Kim H, Choi H, Park J, Kim M, Lee H, Petersen R, et al. Regulation of RhoA activity by the cellular prion protein. Cell Death Dis. 2017;8:e2668 pubmed publisher
  10. Sargent D, Verchère J, Lazizzera C, Gaillard D, Lakhdar L, Streichenberger N, et al. 'Prion-like' propagation of the synucleinopathy of M83 transgenic mice depends on the mouse genotype and type of inoculum. J Neurochem. 2017;143:126-135 pubmed publisher
    ..This acceleration, however, depends on the levels of ?-syn expression by the mouse and the type of inoculum. ..
  11. Matej R, Kovacs G, Johanidesová S, Keller J, Matejckova M, Novakova J, et al. Genetic Creutzfeldt-Jakob disease with R208H mutation presenting as progressive supranuclear palsy. Mov Disord. 2012;27:476-9 pubmed publisher
  12. Boulay G, Sandoval G, Riggi N, Iyer S, Buisson R, Naigles B, et al. Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain. Cell. 2017;171:163-178.e19 pubmed publisher
    ..Our studies thus demonstrate that the physical properties of prion-like domains can retarget critical chromatin regulatory complexes to establish and maintain oncogenic gene expression programs. ..
  13. Brandner S. Diversity of prion diseases: (no) strains attached?. Acta Neuropathol. 2011;121:1-4 pubmed publisher
  14. Moore S, West Greenlee M, Kondru N, Manne S, Smith J, Kunkle R, et al. Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation. J Virol. 2017;91: pubmed publisher
    ..Regardless, positive results obtained with orally inoculated pigs suggest that it may be possible for swine to serve as a reservoir for prion disease under natural conditions. ..
  15. Henderson D, Tennant J, Haley N, Denkers N, Mathiason C, Hoover E. Detection of chronic wasting disease prion seeding activity in deer and elk feces by real-time quaking-induced conversion. J Gen Virol. 2017;98:1953-1962 pubmed publisher
    ..The results have application to detection, surveillance and management of CWD, and potentially to other protein-misfolding diseases. ..
  16. Harrison A, Shorter J. RNA-binding proteins with prion-like domains in health and disease. Biochem J. 2017;474:1417-1438 pubmed publisher
    ..We also highlight the potential of protein disaggregases, including Hsp104, as a therapeutic strategy to combat the aberrant phase transitions of RBPs with PrLDs that likely underpin neurodegeneration. ..
  17. Popko B. Myelin maintenance: axonal support required. Nat Neurosci. 2010;13:275-7 pubmed publisher
  18. de Brito G, Lupinacci F, Beraldo F, Santos T, Roffe M, Lopes M, et al. Loss of prion protein is associated with the development of insulin resistance and obesity. Biochem J. 2017;474:2981-2991 pubmed publisher
    ..Thus, our results suggest that PrPC reflects susceptibility to the development of insulin resistance and metabolic syndrome. ..
  19. Sengupta I, Udgaonkar J. Expression and purification of single cysteine-containing mutant variants of the mouse prion protein by oxidative refolding. Protein Expr Purif. 2017;140:1-7 pubmed publisher
    ..The current strategy facilitates sample preparation for a number of high resolution spectroscopic measurements for the prion protein, which specifically require thiol labelling. ..
  20. Salazar S, Gallardo C, Kaufman A, Herber C, Haas L, Robinson S, et al. Conditional Deletion of Prnp Rescues Behavioral and Synaptic Deficits after Disease Onset in Transgenic Alzheimer's Disease. J Neurosci. 2017;37:9207-9221 pubmed publisher
    ..This study underscores the therapeutic potential of PrPC deletion given that patients already present symptoms at the time of diagnosis. ..
  21. Weissmann C. Mutation and selection of prions. PLoS Pathog. 2012;8:e1002582 pubmed publisher
  22. Batlle C, Fernández M, Iglesias V, Ventura S. Perfecting prediction of mutational impact on the aggregation propensity of the ALS-associated hnRNPA2 prion-like protein. FEBS Lett. 2017;591:1966-1971 pubmed publisher
    ..This opens an avenue for the prediction of disease causing mutations in other human prion-like proteins. ..
  23. Massignan T, Sangiovanni V, Biggi S, Stincardini C, Elezgarai S, Maietta G, et al. A Small-Molecule Inhibitor of Prion Replication and Mutant Prion Protein Toxicity. ChemMedChem. 2017;12:1286-1292 pubmed publisher
    ..Compound 55 may represent the starting point for the development of a completely new class of therapeutics for prion diseases. ..
  24. Groveman B, Raymond G, Campbell K, Race B, Raymond L, Hughson A, et al. Role of the central lysine cluster and scrapie templating in the transmissibility of synthetic prion protein aggregates. PLoS Pathog. 2017;13:e1006623 pubmed publisher
    ..We confirm that some rPrP aggregates can initiate further aggregation without typical pathogenesis in vivo. We also provide evidence that there is little, if any, biohazard associated with routine RT-QuIC assays. ..
  25. Head M, Lowrie S, Chohan G, Knight R, Scoones D, Ironside J. Variably protease-sensitive prionopathy in a PRNP codon 129 heterozygous UK patient with co-existing tau, ? synuclein and A? pathology. Acta Neuropathol. 2010;120:821-3 pubmed publisher
  26. Hannaoui S, Amidian S, Cheng Y, Duque Velasquez C, Dorosh L, Law S, et al. Destabilizing polymorphism in cervid prion protein hydrophobic core determines prion conformation and conversion efficiency. PLoS Pathog. 2017;13:e1006553 pubmed publisher
    ..Therefore, a thorough analysis of CWD isolates and re-assessment of species-barriers is important in order to fully exclude a zoonotic potential of CWD. ..
  27. Thackray A, Cardova A, Wolf H, Pradl L, Vorberg I, Jackson W, et al. Genetic human prion disease modelled in PrP transgenic Drosophila. Biochem J. 2017;474:3253-3267 pubmed publisher
  28. Davenport K, Hoover C, Bian J, Telling G, Mathiason C, Hoover E. PrPC expression and prion seeding activity in the alimentary tract and lymphoid tissue of deer. PLoS ONE. 2017;12:e0183927 pubmed publisher
    ..These data suggest that PrPC expression is not the sole driver of prion accumulation and that alimentary tract tissues accumulate prions before centrifugal spread from the brain occurs. ..
  29. Küffer A, Lakkaraju A, Mogha A, Petersen S, Airich K, Doucerain C, et al. The prion protein is an agonistic ligand of the G protein-coupled receptor Adgrg6. Nature. 2016;536:464-8 pubmed
    ..As well as clarifying the physiological role of PrP(C), these observations are relevant to the pathogenesis of demyelinating polyneuropathies--common debilitating diseases for which there are limited therapeutic options. ..
  30. Mahmud M, Oda M, Usui D, Inoshima Y, Ishiguro N, Kamatari Y. A multispecific monoclonal antibody G2 recognizes at least three completely different epitope sequences with high affinity. Protein Sci. 2017;26:2162-2169 pubmed publisher
  31. Haley N, Rielinger R, Davenport K, O Rourke K, Mitchell G, Richt J. Estimating chronic wasting disease susceptibility in cervids using real-time quaking-induced conversion. J Gen Virol. 2017;98:2882-2892 pubmed publisher
  32. Hamdan N, Kritsiligkou P, Grant C. ER stress causes widespread protein aggregation and prion formation. J Cell Biol. 2017;216:2295-2304 pubmed publisher
    ..The onset of ER stress is known to correlate with various disease processes, and our data indicate that widespread amorphous and amyloid protein aggregation is an unanticipated outcome of such stress. ..
  33. Nuvolone M, Paolucci M, Sorce S, Kana V, Moos R, Matozaki T, et al. Prion pathogenesis is unaltered in the absence of SIRP?-mediated "don't-eat-me" signaling. PLoS ONE. 2017;12:e0177876 pubmed publisher
    ..It will be important to search for additional candidates mediating prion phagocytosis, as this mechanism may represent an important target of antiprion therapies. ..
  34. Sengupta I, Bhate S, Das R, Udgaonkar J. Salt-Mediated Oligomerization of the Mouse Prion Protein Monitored by Real-Time NMR. J Mol Biol. 2017;429:1852-1872 pubmed publisher
    ..Together, these results allowed a demarcation of the specific and non-specific effects of salt on prion protein misfolding and oligomerization. ..
  35. Megra B, Eugenin E, Berman J. The Role of Shed PrPc in the Neuropathogenesis of HIV Infection. J Immunol. 2017;199:224-232 pubmed publisher
    ..We propose that shedding of PrPc could be a potential target for therapeutics to limit the cognitive impairment characteristic of neuroAIDS. ..
  36. Sontag E, Samant R, Frydman J. Mechanisms and Functions of Spatial Protein Quality Control. Annu Rev Biochem. 2017;86:97-122 pubmed publisher
    ..Spatial sequestration plays a central role in protein quality control and cellular fitness and represents a critical link to the pathogenesis of protein aggregation-linked diseases. ..
  37. Jansen C, Parchi P, Jelles B, Gouw A, Beunders G, van Spaendonk R, et al. The first case of fatal familial insomnia (FFI) in the Netherlands: a patient from Egyptian descent with concurrent four repeat tau deposits. Neuropathol Appl Neurobiol. 2011;37:549-53 pubmed publisher
  38. Valtierra S, Du Z, Li L. Analysis of Small Critical Regions of Swi1 Conferring Prion Formation, Maintenance, and Transmission. Mol Cell Biol. 2017;37: pubmed publisher
    ..This PrD is unique in size and composition: glutamine free, asparagine rich, and the smallest defined to date. Our findings broaden our understanding of what features allow a protein region to serve as a PrD. ..
  39. De Strooper B, Simons M, Multhaup G, Van Leuven F, Beyreuther K, Dotti C. Production of intracellular amyloid-containing fragments in hippocampal neurons expressing human amyloid precursor protein and protection against amyloidogenesis by subtle amino acid substitutions in the rodent sequence. EMBO J. 1995;14:4932-8 pubmed
    ..abstract truncated at 250 words) ..