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2000
Volume 20, Issue 3
  • ISSN: 1574-3624
  • E-ISSN: 2212-389X

Abstract

Health concerns have become increasingly prominent in society, with even minor injuries demonstrating an exaggerated potential for complications. This phenomenon parallels an unrelated yet historically significant observation from the 18th century, wherein Merino sheep exhibited abnormal behavioural manifestations indicative of a mysterious ailment. Upon further scientific investigation, this condition was identified as the first recorded instance of a novel class of neurodegenerative disorders now classified as prion diseases, or transmissible spongiform encephalopathies (TSEs), which are brought on by aberrant folding of the brain's cellular prion protein (PrPc). Rapidly progressive neurodegenerative disorders due to prion disease can be seen that can be tough to analyse and are transmissible under certain circumstances. Transmissible spongiform encephalopathies, sometimes known as prion diseases, are a fatal class of inherited, spontaneous, and epidemic neurodegenerative illnesses that affect both humans and animals. Prion disease arises in three ways: acquired or sporadic, inherited, or causal. Many pharmacological techniques and therapies aimed at various stages of the illness progression have been developed and assessed over an extended period, with a select number making progress in clinical trials. As yet, there are no helpful treatment medications authorised for prion illnesses. This paper contains a comprehensive study of the prion protein, prion disease, and different types of prion disease found in animals and humans. The mechanism of this disease, as well as its detection, diagnosis, treatment, and prevention, is discussed in this article.

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References

  1. SigurdsonC.J. BartzJ.C. GlatzelM. Cellular and molecular mechanisms of prion disease.Annu. Rev. Pathol.201914149751610.1146/annurev‑pathmechdis‑012418‑013109 30355150
    [Google Scholar]
  2. LinsenmeierL. MohammadiB. WetzelS. Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein.Mol. Neurodegener.20181311810.1186/s13024‑018‑0248‑6 29625583
    [Google Scholar]
  3. BartzJ.C. Prion strain diversity.Cold Spring Harb. Perspect. Med.2016612a02434910.1101/cshperspect.a024349 27908925
    [Google Scholar]
  4. RitchieD.L. IronsideJ.W. Neuropathology of human prion diseases.Prog. Mol. Biol. Transl. Sci.201715031933910.1016/bs.pmbts.2017.06.011 28838666
    [Google Scholar]
  5. TakadaL.T. GeschwindM.D. Prion diseases.Seminars in neurology.Thieme Medical Publishers201310.1055/s‑0033‑1359314
    [Google Scholar]
  6. WellsG. A novel progressive spongiform encephalopathy in cattle.Vet. Rec.19871211841942010.1136/vr.121.18.419 3424605
    [Google Scholar]
  7. UrwinP.J. MolesworthA.M. The neuroepidemiology of human prion disease.Oxford Textbook of Neurologic and Neuropsychiatric Epidemiology.OxfordAcademic2020367
    [Google Scholar]
  8. SimmonsMM Sheep2011
    [Google Scholar]
  9. BenestadS.L. TellingG.C. Chronic wasting disease: An evolving prion disease of cervids.Handbook of clinical neurology.Elsevier2018135151
    [Google Scholar]
  10. RitchieD.L. BarriaM.A. Prion diseases: A unique transmissible agent or a model for neurodegenerative diseases?Biomolecules202111220710.3390/biom11020207 33540845
    [Google Scholar]
  11. SotoC. PritzkowS. Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases.Nat. Neurosci.201821101332134010.1038/s41593‑018‑0235‑9 30250260
    [Google Scholar]
  12. ScheckelC. AguzziA. Prions, prionoids and protein misfolding disorders.Nat. Rev. Genet.201819740541810.1038/s41576‑018‑0011‑4 29713012
    [Google Scholar]
  13. OmwansuW. MusembiR. DereseS. Structural characterization of codon 129 polymorphism in prion peptide segments (PrP127-132) using the Markov State Models.J. Mol. Graph. Model.202513510892710.1016/j.jmgm.2024.108927 39746241
    [Google Scholar]
  14. GherardiniL. Editorial: New insights into intracellular pathways and therapeutic targets in CNS diseases.Front. Cell. Neurosci.202519155982110.3389/fncel.2025.1559821 39968391
    [Google Scholar]
  15. HornbergerA. The yeast prion domain Sup35 NM models features of human neurodegenerative diseases in vivo.Prion Cell Biology2024
    [Google Scholar]
  16. WengerK. Uncovering the limitations and potential of Alzheimer's disease mouse models using mass spectrometry-based proteomics.Doctoral Thesis2024
    [Google Scholar]
  17. ColesN.P. ElsheikhS. QuesnelA. Molecular insights into α-synuclein fibrillation: A raman spectroscopy and machine learning approach.ACS Chem. Neurosci.202516468769810.1021/acschemneuro.4c00726 39875340
    [Google Scholar]
  18. NizhnikovA. Amyloids and neurodegeneration: More complex than it seems.Pers Psychiatry Neurol20244212
    [Google Scholar]
  19. YiL.X. TanE.K. ZhouZ.D. The α-synuclein seeding amplification assay for Parkinson’s disease.Int. J. Mol. Sci.202526138910.3390/ijms26010389 39796243
    [Google Scholar]
  20. BaiardiS. MammanaA. CapellariS. ParchiP. Human prion disease: Molecular pathogenesis, and possible therapeutic targets and strategies.Expert Opin. Ther. Targets202327121271128410.1080/14728222.2023.2199923 37334903
    [Google Scholar]
  21. SeneffS. KyriakopoulosA.M. NighG. McCulloughP.A. A potential role of the spike protein in neurodegenerative diseases: A narrative review.Cureus2023152e3487210.7759/cureus.34872 36788995
    [Google Scholar]
  22. JellingerK.A. Challenges in the morphological diagnosis of dementias. A. JellingerK Front Clin Drug Res – Alzheimer Disord2013136741010.2174/9781608057221113010012
    [Google Scholar]
  23. SafarJ.G. Molecular pathogenesis of sporadic prion diseases in man.Prion20126210811510.4161/pri.18666 22421210
    [Google Scholar]
  24. NotariS. ApplebyB.S. GambettiP. Variably protease-sensitive prionopathy.Handbook of clinical neurology.Elsevier2018175190
    [Google Scholar]
  25. KovácsG.G. PuopoloM. LadoganaA. Genetic prion disease: The EUROCJD experience.Hum. Genet.2005118216617410.1007/s00439‑005‑0020‑1 16187142
    [Google Scholar]
  26. WangH. RhoadsD.D. ApplebyB.S. Human prion diseases.Curr. Opin. Infect. Dis.201932327227610.1097/QCO.0000000000000552 31008724
    [Google Scholar]
  27. SeedC.R. HewittP.E. DoddR.Y. HoustonF. CervenakovaL. Creutzfeldt‐Jakob disease and blood transfusion safety.Vox Sang.2018113322023110.1111/vox.12631 29359329
    [Google Scholar]
  28. NafeR. ArendtC.T. HattingenE. Human prion diseases and the prion protein – What is the current state of knowledge?Transl. Neurosci.20231412022031510.1515/tnsci‑2022‑0315 37854584
    [Google Scholar]
  29. HoustonF. AndréolettiO. The zoonotic potential of animal prion diseases.Handbook of clinical neurology.Elsevier2018447462
    [Google Scholar]
  30. ShirD. LazarE.B. Graff-RadfordJ. Analysis of clinical features, diagnostic tests, and biomarkers in patients with suspected Creutzfeldt-Jakob disease, 2014-2021.JAMA Netw. Open202258e222509810.1001/jamanetworkopen.2022.25098 35921110
    [Google Scholar]
  31. KishidaH. UedaN. TanakaF. The advances in the early and accurate diagnosis of Creutzfeldt–Jakob disease and other prion diseases: Where are we today?Expert Rev. Neurother.202323980381710.1080/14737175.2023.2246653 37581576
    [Google Scholar]
  32. TesarA. MatejR. KukalJ. Clinical variability in P102L Gerstmann-Sträussler-Scheinker syndrome.Ann. Neurol.201986564365210.1002/ana.25579 31397917
    [Google Scholar]
  33. CraccoL. ApplebyB.S. GambettiP. Fatal familial insomnia and sporadic fatal insomnia.Handbook of clinical neurology.Elsevier2018271299
    [Google Scholar]
  34. SaboowalaH.K. What is Kuru? A Deadly First Human Prion (misfolded proteins).Disease. Dr. Hakim Saboowala2021
    [Google Scholar]
  35. GilchS. SchätzlH.M. New developments in prion disease research.Cell Tissue Res.202339211510.1007/s00441‑023‑03760‑y 36918429
    [Google Scholar]
  36. AndrewsA.H. BloweyR.W. BoydH. EddyR.G. Bovine medicine: diseases and husbandry of cattle.John Wiley & Sons2008
    [Google Scholar]
  37. BeekesM. McBrideP.A. The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies.FEBS J.2007274358860510.1111/j.1742‑4658.2007.05631.x 17288548
    [Google Scholar]
  38. MathiasonC.K. Large animal models for chronic wasting disease.Cell Tissue Res.20233921213110.1007/s00441‑022‑03590‑4 35113219
    [Google Scholar]
  39. CassmannE. MooreS.J. KokemullerR. Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ.BMC Vet. Res.202016138310.1186/s12917‑020‑02611‑0 33032590
    [Google Scholar]
  40. DemierreS. Feline spongiform encephalopathy: First clinical case in Switzerland.Schweiz. Arch. Tierheilkd.20021441055055710.1024/0036‑7281.144.10.550 12442705
    [Google Scholar]
  41. SwireE. ColchesterA. Out of sight, out of mind? BSE 30 years on: Continuing environmental risks to human health.Land Use Policy202312610652110.1016/j.landusepol.2022.106521
    [Google Scholar]
  42. AuthorityE.F.S. The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSE) in 2022.EFSA J.20232111e08384 38035139
    [Google Scholar]
  43. BalamuralidharaV. Transmissible spongiform encephalopathy and its regulations.Indian J Phar Edu Res2023571ss7s1210.5530/ijper.57.1s.2
    [Google Scholar]
  44. KimH.H. KimY.C. KimK. KimA.D. JeongB.H. Novel polymorphisms and genetic features of the Prion Protein Gene (Prnp) in cats, hosts of feline spongiform encephalopathy.Genes20201211310.3390/genes12010013 33374431
    [Google Scholar]
  45. BetancorM. MarínB. OteroA. Detection of classical BSE prions in asymptomatic cows after inoculation with atypical/Nor98 scrapie.Vet. Res.20235418910.1186/s13567‑023‑01225‑2 37794450
    [Google Scholar]
  46. SibilleP. BéringueV. Prion strain evolution and adaptation.Prion2018
    [Google Scholar]
  47. BaralP.K. YinJ. AguzziA. JamesM.N.G. Transition of the prion protein from a structured cellular form (PrPC) to the infectious scrapie agent (PrPSc).Protein Sci.201928122055206310.1002/pro.3735 31583788
    [Google Scholar]
  48. RossiM. BaiardiS. ParchiP. Understanding prion strains: Evidence from studies of the disease forms affecting humans.Viruses201911430910.3390/v11040309 30934971
    [Google Scholar]
  49. CescattiM. SaverioniD. CapellariS. Analysis of conformational stability of abnormal prion protein aggregates across the spectrum of Creutzfeldt-Jakob disease prions.J. Virol.201690146244625410.1128/JVI.00144‑16 27122583
    [Google Scholar]
  50. PedenA.H. SuleimanS. BarriaM.A. Understanding intra-species and inter-species prion conversion and zoonotic potential using protein misfolding cyclic amplification.Front. Aging Neurosci.20211371645210.3389/fnagi.2021.716452 34413769
    [Google Scholar]
  51. BaiardiS. RossiM. CapellariS. ParchiP. Recent advances in the histo‐molecular pathology of human prion disease.Brain Pathol.201929227830010.1111/bpa.12695 30588685
    [Google Scholar]
  52. SlapšakU. SalzanoG. IlcG. Unique structural features of mule deer prion protein provide insights into chronic wasting disease.ACS Omega2019422199131992410.1021/acsomega.9b02824 31788624
    [Google Scholar]
  53. ZerrI. Prion 2022 Conference abstracts: Pushing the boundaries.Prion20221619525310.1080/19336896.2022.2091286
    [Google Scholar]
  54. MeadS. LloydS. CollingeJ. Genetic factors in mammalian prion diseases.Annu. Rev. Genet.201953111714710.1146/annurev‑genet‑120213‑092352 31537104
    [Google Scholar]
  55. WadsworthJ.D.F. CollingeJ. Molecular pathology of human prion disease.Acta Neuropathol.20111211697710.1007/s00401‑010‑0735‑5 20694796
    [Google Scholar]
  56. ParchiP. StrammielloR. GieseA. KretzschmarH. Phenotypic variability of sporadic human prion disease and its molecular basis: Past, present, and future.Acta Neuropathol.201112119111210.1007/s00401‑010‑0779‑6 21107851
    [Google Scholar]
  57. MastrianniJ.A. The genetics of prion diseases.Genet. Med.201012418719510.1097/GIM.0b013e3181cd7374 20216075
    [Google Scholar]
  58. SchmitzM. DittmarK. LlorensF. Hereditary human prion diseases: An update.Mol. Neurobiol.20175464138414910.1007/s12035‑016‑9918‑y 27324792
    [Google Scholar]
  59. WindlO. GieseA. Schulz-SchaefferW. Molecular genetics of human prion diseases in Germany.Hum. Genet.1999105324425210.1007/s004399900124 10987652
    [Google Scholar]
  60. ApplebyB.S. ShettyS. ElkasabyM. Genetic aspects of human prion diseases.Front. Neurol.202213100305610.3389/fneur.2022.1003056 36277922
    [Google Scholar]
  61. Di FedeG. CataniaM. AtzoriC. Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene.Acta Neuropathol. Commun.20197111110.1186/s40478‑018‑0656‑4 30606247
    [Google Scholar]
  62. LiberskiP.P. GajosA. SikorskaB. LindenbaumS. Kuru, the first human prion disease.Viruses201911323210.3390/v11030232 30866511
    [Google Scholar]
  63. AltunaM. RuizI. ZelayaM.V. MendiorozM. Role of biomarkers for the diagnosis of prion diseases: A narrative review.Medicina202258447310.3390/medicina58040473 35454316
    [Google Scholar]
  64. KovacsG.G. BudkaH. Molecular pathology of human prion diseases.Int. J. Mol. Sci.200910397699910.3390/ijms10030976 19399233
    [Google Scholar]
  65. CollingeJ. Mammalian prions and their wider relevance in neurodegenerative diseases.Nature2016539762821722610.1038/nature20415 27830781
    [Google Scholar]
  66. KurtT.D. BettC. Fernández-BorgesN. Prion transmission prevented by modifying the β2-α2 loop structure of host PrPC.J. Neurosci.20143431022102710.1523/JNEUROSCI.4636‑13.2014 24431459
    [Google Scholar]
  67. KurtT.D. JiangL. Fernández-BorgesN. Human prion protein sequence elements impede cross-species chronic wasting disease transmission.J. Clin. Invest.201512541485149610.1172/JCI79408 25705888
    [Google Scholar]
  68. YimY.I. ParkB.C. YadavalliR. ZhaoX. EisenbergE. GreeneL.E. The multivesicular body is the major internal site of prion conversion.J. Cell Sci.201512871434144310.1242/jcs.165472 25663703
    [Google Scholar]
  69. LindenR. The biological function of the prion protein: A cell surface scaffold of signaling modules.Front. Mol. Neurosci.2017107710.3389/fnmol.2017.00077 28373833
    [Google Scholar]
  70. LinsenmeierL. AltmeppenH.C. WetzelS. MohammadiB. SaftigP. GlatzelM. Diverse functions of the prion protein – Does proteolytic processing hold the key?Biochim. Biophys. Acta Mol. Cell Res.20171864112128213710.1016/j.bbamcr.2017.06.022 28693923
    [Google Scholar]
  71. McKinnonC. GooldR. AndreR. Prion-mediated neurodegeneration is associated with early impairment of the ubiquitin–proteasome system.Acta Neuropathol.2016131341142510.1007/s00401‑015‑1508‑y 26646779
    [Google Scholar]
  72. HetzC. MollereauB. Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases.Nat. Rev. Neurosci.201415423324910.1038/nrn3689 24619348
    [Google Scholar]
  73. TorresM. MatamalaJ.M. Duran-AniotzC. CornejoV.H. FoleyA. HetzC. ER stress signaling and neurodegeneration: At the intersection between Alzheimer’s disease and Prion-related disorders.Virus Res.2015207697510.1016/j.virusres.2014.12.018 25556124
    [Google Scholar]
  74. BettC. LawrenceJ. KurtT.D. Enhanced neuroinvasion by smaller, soluble prions.Acta Neuropathol. Commun.2017513210.1186/s40478‑017‑0430‑z 28431576
    [Google Scholar]
  75. Aguilar-CalvoP. BettC. SevillanoA.M. Generation of novel neuroinvasive prions following intravenous challenge.Brain Pathol.2018286999101110.1111/bpa.12598 29505163
    [Google Scholar]
  76. ZhuS. VictoriaG.S. MarzoL. GhoshR. ZurzoloC. Prion aggregates transfer through tunneling nanotubes in endocytic vesicles.Prion20159212513510.1080/19336896.2015.1025189 25996400
    [Google Scholar]
  77. WangX. GerdesH-H. Transfer of mitochondria via tunneling nanotubes rescues apoptotic PC12 cells.Cell Death Differ.20152271181119110.1038/cdd.2014.211 25571977
    [Google Scholar]
  78. AbounitS. BoussetL. LoriaF. Tunneling nanotubes spread fibrillar α‐synuclein by intercellular trafficking of lysosomes.EMBO J.201635192120213810.15252/embj.201593411 27550960
    [Google Scholar]
  79. JoshiT. AhujaN. The prion basis of progressive neurodegenerative disorders.Interdiscip. Perspect. Infect. Dis.2023202311510.1155/2023/6687264 36825209
    [Google Scholar]
  80. RussoM.J. High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease.Acta Neuropathol. Commun.20219113
    [Google Scholar]
  81. NicholsonE.M. GreenleeJ.J. HwangS. Aqueous extraction of formalin-fixed paraffin-embedded tissue and detection of prion disease using real-time quaking-induced conversion.BMC Res. Notes202417126610.1186/s13104‑024‑06886‑6 39285497
    [Google Scholar]
  82. RallisE. GrechV.S. LotsarisK. TertipiN. SfyriE. KefalaV. Skin and induced pluripotent stem cells as biomarkers for neurodegenerative diseases.Genes20241512150710.3390/genes15121507 39766775
    [Google Scholar]
  83. BollM.C. Muñoz-LópezI. CárdenasG. Ramírez-GarcíaM.Á. Nava-GalánM.G. Yescas-GómezP. Apparent diffusion coefficient measurements. A reliable tool for the diagnosis of Creutzfeldt-Jakob disease.Arch. Med. Res.202556210310410.1016/j.arcmed.2024.103104 39437617
    [Google Scholar]
  84. MoudjouM. ChapuisJ. MekroutiM. Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification.Sci. Rep.2016612911610.1038/srep29116 27384922
    [Google Scholar]
  85. ForloniG. RoiterI. TagliaviniF. Clinical trials of prion disease therapeutics.Curr. Opin. Pharmacol.201944536010.1016/j.coph.2019.04.019 31108459
    [Google Scholar]
  86. RajalingamA. GanjiwaleA. Identification of common genetic factors and immune-related pathways associating more than two autoimmune disorders: Implications on risk, diagnosis, and treatment.Genomics Inform.20242211010.1186/s44342‑024‑00004‑5 38956704
    [Google Scholar]
  87. WaltersT. Movement potential of infectious prions by American crows (corvus brachyrhynchos) in an area endemic for chronic wasting disease.Thesis2025
    [Google Scholar]
  88. MinikelE.V. Quantifying prion disease penetrance using large population control cohorts.Sci. Transl. Med.20168322322ra910.1126/scitranslmed.aad5169 26791950
    [Google Scholar]
  89. MinikelE.V. VallabhS.M. OrsethM.C. Age at onset in genetic prion disease and the design of preventive clinical trials.Neurology2019932e125e13410.1212/WNL.0000000000007745 31171647
    [Google Scholar]
  90. CohenO.S. ChapmanJ. KorczynA.D. Familial Creutzfeldt–Jakob disease with the E200K mutation: Longitudinal neuroimaging from asymptomatic to symptomatic CJD.J. Neurol.2015262360461310.1007/s00415‑014‑7615‑1 25522698
    [Google Scholar]
  91. RudgeP. JaunmuktaneZ. HyareH. Early neurophysiological biomarkers and spinal cord pathology in inherited prion disease.Brain2019142376077010.1093/brain/awy358 30698738
    [Google Scholar]
  92. RaymondG.J. ZhaoH.T. RaceB. Antisense oligonucleotides extend survival of prion-infected mice.JCI Insight2019416e13117510.1172/jci.insight.131175 31361599
    [Google Scholar]
  93. VallabhS.M. MinikelE.V. SchreiberS.L. LanderE.S. Towards a treatment for genetic prion disease: Trials and biomarkers.Lancet Neurol.202019436136810.1016/S1474‑4422(19)30403‑X 32199098
    [Google Scholar]
  94. ZafarS. NoorA. ZerrI. Therapies for prion diseases.Handb. Clin. Neurol.2019165475810.1016/B978‑0‑444‑64012‑3.00004‑6 31727228
    [Google Scholar]
  95. MarciniukK. MäättänenP. TaschukR. Development of a multivalent, PrP(Sc)-specific prion vaccine through rational optimization of three disease-specific epitopes.Vaccine201432171988199710.1016/j.vaccine.2014.01.027 24486363
    [Google Scholar]
  96. TaschukR. MarciniukK. MäättänenP. Safety, specificity and immunogenicity of a PrPSc -specific prion vaccine based on the YYR disease specific epitope.Prion201481515910.4161/pri.27962 24509522
    [Google Scholar]
  97. HernaizA. CobetaP. MarínB. Susceptibility of ovine bone marrow-derived mesenchymal stem cell spheroids to scrapie prion infection.Animals2023136104310.3390/ani13061043 36978584
    [Google Scholar]
  98. SellittoS. Human iPSC Models and Whole-Genome CRISPR Screening in Prion Neurodegeneration.SwitzerlandUniversity of Zurich2025
    [Google Scholar]
  99. ZayedM. JeongB-H. Adipose-derived mesenchymal stem cell secretome attenuates prion protein peptide (106–126)-induced oxidative stress via Nrf2 activation.Stem Cell Rev. Rep.202421258959210.1007/s12015‑024‑10811‑6 39480613
    [Google Scholar]
  100. TeeB.L. Longoria IbarrolaE.M. GeschwindM.D. Prion Diseases.Neurol. Clin.201836486589710.1016/j.ncl.2018.07.005 30366560
    [Google Scholar]
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