KEGG PATHWAY: map05020

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

Disease

H00061

Prion disease

Reference

PMID:27055367

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

PMID:25584786

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

PMID:20889378

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

PMID:27060771

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

PMID:32565065

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

PMID:18245809

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

PMID:15695097

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

PMID:17051207

Authors

Caughey B, Baron GS

Title

Prions and their partners in crime.

Journal

Nature 443:803-10 (2006)
DOI:10.1038/nature05294

Reference

PMID:11592845

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

PMID:17085779

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

PMID:14705136

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

PMID:10398674

Authors

Harris DA

Title

Cellular biology of prion diseases.

Journal

Clin Microbiol Rev 12:429-44 (1999)

Reference

PMID:15890824

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

PMID:27581199

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

PMID:31618844

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

PMID:31795242

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

PMID:30710214

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

PMID:23439666

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

PMID:28643372

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

PMID:29194372

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

PMID:24619348

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

PMID:29476642

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

PMID:21722302

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

PMID:18420416

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

PMID:16844381

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

PMID:21980554

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

PMID:25766616

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

PMID:17466621

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

PMID:10195903

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

PMID:14532116

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

PMID:31417367

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

PMID:29261664

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

PMID:21196165

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

PMID:23479001

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

PMID:28507517

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

PMID:15528202

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

PMID:15640354

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

PMID:20205843

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

PMID:29998397

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

PMID:28714865

Authors

Aguzzi A, Zhu C

Title

Microglia in prion diseases.

Journal

J Clin Invest 127:3230-3239 (2017)
DOI:10.1172/JCI90605