KEGG   PATHWAY: map05020
Entry
map05020                    Pathway                                

Name
Prion disease
Description
Prion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of these diseases is thought to be associated with the conversion of a normal protein, PrPC, into an infectious, pathogenic form, PrPSc. The conversion is induced by prion infections (for example, variant Creutzfeldt-Jakob disease (vCJD), iatrogenic CJD, Kuru), mutations (familial CJD, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia (FFI)) or unknown factors (sporadic CJD (sCJD)), and is thought to occur after PrPC has reached the plasma membrane or is re-internalized for degradation. The PrPSc form shows greater protease resistance than PrPC and accumulates in affected individuals, often in the form of extracellular plaques. Pathways that may lead to neuronal death comprise oxidative stress, regulated activation of complement, ubiquitin-proteasome and endosomal-lysosomal systems, synaptic alterations and dendritic atrophy, corticosteroid response, and endoplasmic reticulum stress. In addition, the conformational transition could lead to the lost of a beneficial activity of the natively folded protein, PrPC.
Class
Human Diseases; Neurodegenerative disease
Pathway map
map05020  Prion disease
map05020

Disease
H00061  Prion disease
Reference
  Authors
Saa P, Harris DA, Cervenakova L
  Title
Mechanisms of prion-induced neurodegeneration.
  Journal
Expert Rev Mol Med 18:e5 (2016)
DOI:10.1017/erm.2016.8
Reference
  Authors
Goold R, McKinnon C, Tabrizi SJ
  Title
Prion degradation pathways: Potential for therapeutic intervention.
  Journal
Mol Cell Neurosci 66:12-20 (2015)
DOI:10.1016/j.mcn.2014.12.009
Reference
  Authors
Soto C, Satani N
  Title
The intricate mechanisms of neurodegeneration in prion diseases.
  Journal
Trends Mol Med 17:14-24 (2011)
DOI:10.1016/j.molmed.2010.09.001
Reference
  Authors
Mays CE, Soto C
  Title
The stress of prion disease.
  Journal
Brain Res 1648:553-560 (2016)
DOI:10.1016/j.brainres.2016.04.009
Reference
  Authors
Jones E, Mead S
  Title
Genetic risk factors for Creutzfeldt-Jakob disease.
  Journal
Neurobiol Dis 142:104973 (2020)
DOI:10.1016/j.nbd.2020.104973
Reference
  Authors
Kovacs GG, Budka H
  Title
Prion diseases: from protein to cell pathology.
  Journal
Am J Pathol 172:555-65 (2008)
DOI:10.2353/ajpath.2008.070442
Reference
  Authors
Campana V, Sarnataro D, Zurzolo C
  Title
The highways and byways of prion protein trafficking.
  Journal
Trends Cell Biol 15:102-11 (2005)
DOI:10.1016/j.tcb.2004.12.002
Reference
  Authors
Caughey B, Baron GS
  Title
Prions and their partners in crime.
  Journal
Nature 443:803-10 (2006)
DOI:10.1038/nature05294
Reference
  Authors
Chiesa R, Harris DA
  Title
Prion diseases: what is the neurotoxic molecule?
  Journal
Neurobiol Dis 8:743-63 (2001)
DOI:10.1006/nbdi.2001.0433
Reference
  Authors
Fasano C, Campana V, Zurzolo C
  Title
Prions: protein only or something more? Overview of potential prion cofactors.
  Journal
J Mol Neurosci 29:195-214 (2006)
DOI:10.1385/JMN:29:3:195
Reference
  Authors
Roucou X, Gains M, LeBlanc AC
  Title
Neuroprotective functions of prion protein.
  Journal
J Neurosci Res 75:153-61 (2004)
DOI:10.1002/jnr.10864
Reference
  Authors
Harris DA
  Title
Cellular biology of prion diseases.
  Journal
Clin Microbiol Rev 12:429-44 (1999)
Reference
  Authors
Novakofski J, Brewer MS, Mateus-Pinilla N, Killefer J, McCusker RH
  Title
Prion biology relevant to bovine spongiform encephalopathy.
  Journal
J Anim Sci 83:1455-76 (2005)
DOI:10.2527/2005.8361455x
Reference
  Authors
Peggion C, Bertoli A, Sorgato MC
  Title
Almost a century of prion protein(s): From pathology to physiology, and back to pathology.
  Journal
Biochem Biophys Res Commun 483:1148-1155 (2017)
DOI:10.1016/j.bbrc.2016.07.118
Reference
  Authors
Ryskalin L, Busceti CL, Biagioni F, Limanaqi F, Familiari P, Frati A, Fornai F
  Title
Prion Protein in Glioblastoma Multiforme.
  Journal
Int J Mol Sci 20:E5107 (2019)
DOI:10.3390/ijms20205107
Reference
  Authors
Ureshino RP, Erustes AG, Bassani TB, Wachilewski P, Guarache GC, Nascimento AC, Costa AJ, Smaili SS, Pereira GJDS
  Title
The Interplay between Ca(2+) Signaling Pathways and Neurodegeneration.
  Journal
Int J Mol Sci 20:E6004 (2019)
DOI:10.3390/ijms20236004
Reference
  Authors
Meneghetti E, Gasperini L, Virgilio T, Moda F, Tagliavini F, Benetti F, Legname G
  Title
Prions Strongly Reduce NMDA Receptor S-Nitrosylation Levels at Pre-symptomatic and Terminal Stages of Prion Diseases.
  Journal
Mol Neurobiol 56:6035-6045 (2019)
DOI:10.1007/s12035-019-1505-6
Reference
  Authors
Song Z, Zhao D, Yang L
  Title
Molecular mechanisms of neurodegeneration mediated by dysfunctional subcellular organelles in transmissible spongiform encephalopathies.
  Journal
Acta Biochim Biophys Sin (Shanghai) 45:452-64 (2013)
DOI:10.1093/abbs/gmt014
Reference
  Authors
Halliday M, Hughes D, Mallucci GR
  Title
Fine-tuning PERK signaling for neuroprotection.
  Journal
J Neurochem 142:812-826 (2017)
DOI:10.1111/jnc.14112
Reference
  Authors
Hughes D, Halliday M
  Title
What Is Our Current Understanding of PrP(Sc)-Associated Neurotoxicity and Its Molecular Underpinnings?
  Journal
Pathogens 6:E63 (2017)
DOI:10.3390/pathogens6040063
Reference
  Authors
Hetz C, Mollereau B
  Title
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases.
  Journal
Nat Rev Neurosci 15:233-49 (2014)
DOI:10.1038/nrn3689
Reference
  Authors
Hughes D, Mallucci GR
  Title
The unfolded protein response in neurodegenerative disorders - therapeutic modulation of the PERK pathway.
  Journal
FEBS J 286:342-355 (2019)
DOI:10.1111/febs.14422
Reference
  Authors
Doyle KM, Kennedy D, Gorman AM, Gupta S, Healy SJ, Samali A
  Title
Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders.
  Journal
J Cell Mol Med 15:2025-39 (2011)
DOI:10.1111/j.1582-4934.2011.01374.x
Reference
  Authors
Ferreiro E, Oliveira CR, Pereira CM
  Title
The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway.
  Journal
Neurobiol Dis 30:331-42 (2008)
DOI:10.1016/j.nbd.2008.02.003
Reference
  Authors
Ferreiro E, Resende R, Costa R, Oliveira CR, Pereira CM
  Title
An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity.
  Journal
Neurobiol Dis 23:669-78 (2006)
DOI:10.1016/j.nbd.2006.05.011
Reference
  Authors
Torres M, Encina G, Soto C, Hetz C
  Title
Abnormal calcium homeostasis and protein folding stress at the ER: A common factor in familial and infectious prion disorders.
  Journal
Commun Integr Biol 4:258-61 (2011)
DOI:10.4161/cib.4.3.15019
Reference
  Authors
Ciechanover A, Kwon YT
  Title
Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies.
  Journal
Exp Mol Med 47:e147 (2015)
DOI:10.1038/emm.2014.117
Reference
  Authors
Kristiansen M, Deriziotis P, Dimcheff DE, Jackson GS, Ovaa H, Naumann H, Clarke AR, van Leeuwen FW, Menendez-Benito V, Dantuma NP, Portis JL, Collinge J, Tabrizi SJ
  Title
Disease-associated prion protein oligomers inhibit the 26S proteasome.
  Journal
Mol Cell 26:175-88 (2007)
DOI:10.1016/j.molcel.2007.04.001
Reference
  Authors
Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC.
  Title
Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD.
  Journal
Science 284:339-43 (1999)
DOI:10.1126/science.284.5412.339
Reference
  Authors
Hetz C, Russelakis-Carneiro M, Maundrell K, Castilla J, Soto C
  Title
Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein.
  Journal
EMBO J 22:5435-45 (2003)
DOI:10.1093/emboj/cdg537
Reference
  Authors
Zamponi E, Pigino GF
  Title
Protein Misfolding, Signaling Abnormalities and Altered Fast Axonal Transport: Implications for Alzheimer and Prion Diseases.
  Journal
Front Cell Neurosci 13:350 (2019)
DOI:10.3389/fncel.2019.00350
Reference
  Authors
Zamponi E, Buratti F, Cataldi G, Caicedo HH, Song Y, Jungbauer LM, LaDu MJ, Bisbal M, Lorenzo A, Ma J, Helguera PR, Morfini GA, Brady ST, Pigino GF
  Title
Prion protein inhibits fast axonal transport through a mechanism involving casein kinase 2.
  Journal
PLoS One 12:e0188340 (2017)
DOI:10.1371/journal.pone.0188340
Reference
  Authors
Schneider B, Pietri M, Pradines E, Loubet D, Launay JM, Kellermann O, Mouillet-Richard S
  Title
Understanding the neurospecificity of Prion protein signaling.
  Journal
Front Biosci (Landmark Ed) 16:169-86 (2011)
DOI:10.2741/3682
Reference
  Authors
Didonna A
  Title
Prion protein and its role in signal transduction.
  Journal
Cell Mol Biol Lett 18:209-30 (2013)
DOI:10.2478/s11658-013-0085-0
Reference
  Authors
Shah SZA, Zhao D, Hussain T, Yang L
  Title
The Role of Unfolded Protein Response and Mitogen-Activated Protein Kinase Signaling in Neurodegenerative Diseases with Special Focus on Prion Diseases.
  Journal
Front Aging Neurosci 9:120 (2017)
DOI:10.3389/fnagi.2017.00120
Reference
  Authors
Marella M, Gaggioli C, Batoz M, Deckert M, Tartare-Deckert S, Chabry J
  Title
Pathological prion protein exposure switches on neuronal mitogen-activated protein kinase pathway resulting in microglia recruitment.
  Journal
J Biol Chem 280:1529-34 (2005)
DOI:10.1074/jbc.M410966200
Reference
  Authors
Ishikura N, Clever JL, Bouzamondo-Bernstein E, Samayoa E, Prusiner SB, Huang EJ, DeArmond SJ
  Title
Notch-1 activation and dendritic atrophy in prion disease.
  Journal
Proc Natl Acad Sci U S A 102:886-91 (2005)
DOI:10.1073/pnas.0408612101
Reference
  Authors
Dearmond SJ, Bajsarowicz K
  Title
PrPSc accumulation in neuronal plasma membranes links Notch-1 activation to dendritic degeneration in prion diseases.
  Journal
Mol Neurodegener 5:6 (2010)
DOI:10.1186/1750-1326-5-6
Reference
  Authors
Hirsch TZ, Martin-Lanneree S, Reine F, Hernandez-Rapp J, Herzog L, Dron M, Privat N, Passet B, Halliez S, Villa-Diaz A, Lacroux C, Klein V, Haik S, Andreoletti O, Torres JM, Vilotte JL, Beringue V, Mouillet-Richard S
  Title
Epigenetic Control of the Notch and Eph Signaling Pathways by the Prion Protein: Implications for Prion Diseases.
  Journal
Mol Neurobiol 56:2159-2173 (2019)
DOI:10.1007/s12035-018-1193-7
Reference
  Authors
Aguzzi A, Zhu C
  Title
Microglia in prion diseases.
  Journal
J Clin Invest 127:3230-3239 (2017)
DOI:10.1172/JCI90605
Reference
  Authors
Mabbott NA
  Title
The complement system in prion diseases.
  Journal
Curr Opin Immunol 16:587-93 (2004)
DOI:10.1016/j.coi.2004.07.002
Reference
  Authors
Mallucci G, Collinge J
  Title
Rational targeting for prion therapeutics.
  Journal
Nat Rev Neurosci 6:23-34 (2005)
DOI:10.1038/nrn1584
Related
pathway
map00190  Oxidative phosphorylation
map03050  Proteasome
map04020  Calcium signaling pathway
map04140  Autophagy - animal
map04141  Protein processing in endoplasmic reticulum
map04142  Lysosome
map04144  Endocytosis
map04210  Apoptosis
map04330  Notch signaling pathway
map04610  Complement and coagulation cascades
map04668  TNF signaling pathway
KO pathway
ko05020   

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