Progress and Problems in the Biology, Diagnostics, and Therapeutics of Prion Diseases

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2004 Jul 16

PMID 15254579

Citations 19

Authors

Adriano Aguzzi

Mathias Heikenwalder

Gino Miele

Affiliations

Soon will be listed here.

Abstract

The term "prion" was introduced by Stanley Prusiner in 1982 to describe the atypical infectious agent that causes transmissible spongiform encephalopathies, a group of infectious neurodegenerative diseases that include scrapie in sheep, Creutzfeldt-Jakob disease in humans, chronic wasting disease in cervids, and bovine spongiform encephalopathy in cattle. Over the past twenty years, the word "prion" has been taken to signify various subtly different concepts. In this article, we refer to the prion as the transmissible principle underlying prion diseases, without necessarily implying any specific biochemical or structural identity. When Prusiner started his seminal work, the study of transmissible spongiform encephalopathies was undertaken by only a handful of scientists. Since that time, the "mad cow" crisis has put prion diseases on the agenda of both politicians and the media. Significant progress has been made in prion disease research, and many aspects of prion pathogenesis are now understood. And yet the diagnostic procedures available for prion diseases are not nearly as sensitive as they ought to be, and no therapeutic intervention has been shown to reliably affect the course of the diseases. This article reviews recent progress in the areas of pathogenesis of, diagnostics of, and therapy for prion diseases and highlights some conspicuous problems that remain to be addressed in each of these fields.

Citing Articles

Oral administration of repurposed drug targeting Cyp46A1 increases survival times of prion infected mice.

Ali T, Hannaoui S, Nemani S, Tahir W, Zemlyankina I, Cherry P Acta Neuropathol Commun. 2021; 9(1):58.

PMID: 33795005 PMC: 8017635. DOI: 10.1186/s40478-021-01162-1.

Detection of Pathognomonic Biomarker PrP and the Contribution of Cell Free-Amplification Techniques to the Diagnosis of Prion Diseases.

Erana H, Charco J, Gonzalez-Miranda E, Garcia-Martinez S, Lopez-Moreno R, Perez-Castro M Biomolecules. 2020; 10(3).

PMID: 32204429 PMC: 7175149. DOI: 10.3390/biom10030469.

Prions Strongly Reduce NMDA Receptor S-Nitrosylation Levels at Pre-symptomatic and Terminal Stages of Prion Diseases.

Meneghetti E, Gasperini L, Virgilio T, Moda F, Tagliavini F, Benetti F Mol Neurobiol. 2019; 56(9):6035-6045.

PMID: 30710214 DOI: 10.1007/s12035-019-1505-6.

Ultra-efficient Amplification of Abnormal Prion Protein by Modified Protein Misfolding Cyclic Amplification with Electric Current.

Park J, Choi Y, Park S, Choi H, Choi E, Kim Y Mol Neurobiol. 2017; 55(2):1630-1638.

PMID: 28194643 PMC: 5820375. DOI: 10.1007/s12035-017-0431-8.

Prions in dentistry: A need to be concerned and known.

Sushma B, Gugwad S, Pavaskar R, Malik S J Oral Maxillofac Pathol. 2016; 20(1):111-4.

PMID: 27194872 PMC: 4860911. DOI: 10.4103/0973-029X.180961.

References

Brown K, Stewart K, Ritchie D, Mabbott N, Williams A, Fraser H . Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells. Nat Med. 1999; 5(11):1308-12. DOI: 10.1038/15264. View

Safar J, Scott M, Monaghan J, Deering C, Didorenko S, Vergara J . Measuring prions causing bovine spongiform encephalopathy or chronic wasting disease by immunoassays and transgenic mice. Nat Biotechnol. 2002; 20(11):1147-50. DOI: 10.1038/nbt748. View

Peretz D, Williamson R, Kaneko K, Vergara J, Leclerc E, Schmitt-Ulms G . Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature. 2001; 412(6848):739-43. DOI: 10.1038/35089090. View

Brandner S, Raeber A, Sailer A, Blattler T, Fischer M, Weissmann C . Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system. Proc Natl Acad Sci U S A. 1996; 93(23):13148-51. PMC: 24061. DOI: 10.1073/pnas.93.23.13148. View

Duguid J, Trzepacz C . Major histocompatibility complex genes have an increased brain expression after scrapie infection. Proc Natl Acad Sci U S A. 1993; 90(1):114-7. PMC: 45610. DOI: 10.1073/pnas.90.1.114. View

Korth C, May B, Cohen F, Prusiner S . Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc Natl Acad Sci U S A. 2001; 98(17):9836-41. PMC: 55539. DOI: 10.1073/pnas.161274798. View

Souan L, Tal Y, Felling Y, Cohen I, Taraboulos A, Mor F . Modulation of proteinase-K resistant prion protein by prion peptide immunization. Eur J Immunol. 2001; 31(8):2338-46. DOI: 10.1002/1521-4141(200108)31:8<2338::aid-immu2338>3.0.co;2-v. View

Bolton D, McKinley M, Prusiner S . Identification of a protein that purifies with the scrapie prion. Science. 1982; 218(4579):1309-11. DOI: 10.1126/science.6815801. View

Zeidler M, Collie D, MacLeod M, Sellar R, Knight R . FLAIR MRI in sporadic Creutzfeldt-Jakob disease. Neurology. 2001; 56(2):282. DOI: 10.1212/wnl.56.2.282. View

10.

Collins S, Lawson V, Masters C . Transmissible spongiform encephalopathies. Lancet. 2004; 363(9402):51-61. DOI: 10.1016/S0140-6736(03)15171-9. View

11.

Priola S, Raines A, Caughey W . Porphyrin and phthalocyanine antiscrapie compounds. Science. 2000; 287(5457):1503-6. DOI: 10.1126/science.287.5457.1503. View

12.

Brandner S, Isenmann S, Raeber A, Fischer M, Sailer A, Kobayashi Y . Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature. 1996; 379(6563):339-43. DOI: 10.1038/379339a0. View

13.

Griffith J . Self-replication and scrapie. Nature. 1967; 215(5105):1043-4. DOI: 10.1038/2151043a0. View

14.

Glock B, Winter M, Rennhofer S, Brunholzl E, Troscher D, Reisacher R . Transcript level of erythroid differentiation-related factor, a candidate surrogate marker for transmissible spongiform encephalopathy diseases in blood, shows a broad range of variation in healthy individuals. Transfusion. 2003; 43(12):1706-10. DOI: 10.1111/j.0041-1132.2003.00575.x. View

15.

Enari M, Flechsig E, Weissmann C . Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody. Proc Natl Acad Sci U S A. 2001; 98(16):9295-9. PMC: 55414. DOI: 10.1073/pnas.151242598. View

16.

Mallucci G, Dickinson A, Linehan J, Klohn P, Brandner S, Collinge J . Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science. 2003; 302(5646):871-4. DOI: 10.1126/science.1090187. View

17.

Mead S, Stumpf M, Whitfield J, Beck J, Poulter M, Campbell T . Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science. 2003; 300(5619):640-3. DOI: 10.1126/science.1083320. View

18.

Aguzzi A, Montrasio F, Kaeser P . Prions: health scare and biological challenge. Nat Rev Mol Cell Biol. 2001; 2(2):118-26. DOI: 10.1038/35052063. View

19.

Glatzel M, Abela E, Maissen M, Aguzzi A . Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med. 2003; 349(19):1812-20. DOI: 10.1056/NEJMoa030351. View

20.

Hegde R, Mastrianni J, Scott M, DeFea K, Tremblay P, Torchia M . A transmembrane form of the prion protein in neurodegenerative disease. Science. 1998; 279(5352):827-34. DOI: 10.1126/science.279.5352.827. View