Details of Disease

General Information of Disease (ID: DISOUMB0)

• Disease Name: Prion disease
• Synonyms: prion disease pathway; spongiform encephalopathy; prion protein disease; prion induced disorder
• Definition: A transmissible disease that is caused by a protein that is able to induce abnormal folding of normal cellular proteins, leading to characteristic spongiform brain changes, which are associated with neuronal loss without an inflammatory response. Such disorders have typically long incubation periods, but are then generally rapidly progressive and are uniformly fatal.|Editor note: check relationship to spongiform encephalopathy NCIT:C27585
• Disease Hierarchy:
  DISF1QLJ: Central nervous system infectious disorder
  DISWD40R: Disease
  DIS6ZC3X: Brain disease
  DISOUMB0: Prion disease
• Disease Identifiers:
  MONDO ID: MONDO_0005429
  MESH ID: D017096
  UMLS CUI: C0162534
  MedGen ID: 56445
  SNOMED CT ID: 20484008

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 14 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CLU	TTRL76H	Limited	Genetic Variation	[1]
ADAM10	TTVXEGU	Strong	Biomarker	[2]
C9orf72	TTA4SHR	Strong	Genetic Variation	[1]
CHN2	TT39YVO	Strong	Genetic Variation	[1]
CHRM1	TTZ9SOR	Strong	Genetic Variation	[3]
CR2	TT0HUN7	Strong	Biomarker	[4]
CX3CL1	TT1OFBQ	Strong	Biomarker	[5]
CX3CR1	TT2T98G	Strong	Biomarker	[5]
FKBP10	TT4P8O2	Strong	Biomarker	[6]
GPI	TT19JIZ	Strong	Altered Expression	[7]
GSS	TTVEWR4	Strong	Biomarker	[8]
IAPP	TTHN8EM	Strong	Biomarker	[9]
SIRPA	TTBRJS9	Strong	Biomarker	[10]
SNCA	TT08OSU	Strong	Biomarker	[11]

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCA7	DTDVSJA	Strong	Genetic Variation	[1]
ABCB6	DTF9Y2V	Strong	Genetic Variation	[12]
SLC2A13	DT0NSKB	Strong	Genetic Variation	[1]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
FXN	DEXVHDB	Strong	Biomarker	[13]

This Disease Is Related to 39 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MARK4	OT6Z2TGV	Limited	Genetic Variation	[1]
ANK3	OTJ3IRBP	moderate	Genetic Variation	[14]
AKT1S1	OT4JHN4Y	Strong	Biomarker	[15]
BAG6	OT4Z0S2U	Strong	Altered Expression	[16]
BLOC1S3	OTNRFFLW	Strong	Genetic Variation	[1]
BST1	OTAV5SE7	Strong	Genetic Variation	[1]
C4BPA	OTHNH6Y8	Strong	Genetic Variation	[12]
CALHM1	OTUZPEYQ	Strong	Biomarker	[17]
CARD14	OTADQHOV	Strong	Genetic Variation	[12]
CBLL2	OTB4AD3V	Strong	Biomarker	[18]
CCDC62	OTTIAOBP	Strong	Genetic Variation	[1]
CD2AP	OTC76KQM	Strong	Genetic Variation	[1]
CHN1	OTM196M3	Strong	Genetic Variation	[19]
CPNE8	OTO6U97G	Strong	Altered Expression	[20]
CST7	OTQWZUVQ	Strong	Biomarker	[21]
HSPA13	OTYXMC4G	Strong	Genetic Variation	[22]
IGFALS	OTTWCZYM	Strong	Biomarker	[23]
KARS1	OT0EU4SV	Strong	Genetic Variation	[24]
LAMA3	OTFME7HT	Strong	Genetic Variation	[24]
LRFN5	OTK7QZ3B	Strong	Biomarker	[19]
MKLN1	OTHMIMH6	Strong	Biomarker	[25]
MS4A4A	OTWV82RP	Strong	Genetic Variation	[1]
MUL1	OT2JC9YR	Strong	Biomarker	[18]
NEFL	OTQESJV4	Strong	Biomarker	[26]
NEGR1	OT57ECW9	Strong	Biomarker	[27]
PDIK1L	OTISF4KG	Strong	Biomarker	[28]
PLCXD3	OTJNSWMU	Strong	Genetic Variation	[29]
PLK3	OT19CT2Z	Strong	Biomarker	[30]
PPP1R12B	OTONIS87	Strong	Genetic Variation	[1]
PRDX2	OTLWCY9T	Strong	Genetic Variation	[12]
PRND	OTH4EEMI	Strong	Biomarker	[31]
SARM1	OTEP4I5O	Strong	Biomarker	[32]
SEC61A1	OTLBE3CB	Strong	Biomarker	[33]
SERPINA3	OT9BP2S0	Strong	Biomarker	[34]
SNCB	OTELSEK6	Strong	Biomarker	[35]
SPRN	OTVKSA48	Strong	Genetic Variation	[36]
STMN2	OT0FUHLH	Strong	Altered Expression	[37]
TOMM40	OTZDQ29F	Strong	Genetic Variation	[1]
TPPP	OTCFMSUF	Strong	Biomarker	[38]

References

• [1] Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP.Hum Mol Genet. 2012 Apr 15;21(8):1897-906. doi: 10.1093/hmg/ddr607. Epub 2011 Dec 30.
• [2] Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein.Mol Neurodegener. 2018 Apr 6;13(1):18. doi: 10.1186/s13024-018-0248-6.
• [3] M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss.J Clin Invest. 2017 Feb 1;127(2):487-499. doi: 10.1172/JCI87526. Epub 2016 Dec 19.
• [4] Relative Impact of Complement Receptors CD21/35 (Cr2/1) on Scrapie Pathogenesis in Mice.mSphere. 2017 Nov 22;2(6):e00493-17. doi: 10.1128/mSphereDirect.00493-17. eCollection 2017 Nov-Dec.
• [5] Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS.Glia. 2002 Mar 15;37(4):314-27.
• [6] Inhibition of the FKBP family of peptidyl prolyl isomerases induces abortive translocation and degradation of the cellular prion protein.Mol Biol Cell. 2016 Mar 1;27(5):757-67. doi: 10.1091/mbc.E15-10-0729. Epub 2016 Jan 13.
• [7] The first report of polymorphisms and genetic characteristics of the prion protein gene (PRNP) in horses.Prion. 2018;12(3-4):245-252. doi: 10.1080/19336896.2018.1513316. Epub 2018 Sep 12.
• [8] Electron microscopic and confocal laser microscopy analysis of amyloid plaques in chronic wasting disease transmitted to transgenic mice.Prion. 2017 Nov 2;11(6):431-439. doi: 10.1080/19336896.2017.1384109.
• [9] Implications of peptide assemblies in amyloid diseases.Chem Soc Rev. 2017 Oct 30;46(21):6492-6531. doi: 10.1039/c7cs00372b.
• [10] Prion pathogenesis is unaltered in the absence of SIRP-mediated "don't-eat-me" signaling.PLoS One. 2017 May 17;12(5):e0177876. doi: 10.1371/journal.pone.0177876. eCollection 2017.
• [11] -Synuclein chaperone suppresses nucleation and amyloidogenesis of prion protein.Biochem Biophys Res Commun. 2020 Jan 1;521(1):259-264. doi: 10.1016/j.bbrc.2019.10.120. Epub 2019 Oct 18.
• [12] PrP(ST), a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.PLoS One. 2013 Jul 26;8(7):e69583. doi: 10.1371/journal.pone.0069583. Print 2013.
• [13] Emergence of breath testing as a new non-invasive diagnostic modality for neurodegenerative diseases.Brain Res. 2018 Jul 15;1691:75-86. doi: 10.1016/j.brainres.2018.04.017. Epub 2018 Apr 22.
• [14] Genome-wide association study of behavioural and psychiatric features in human prion disease.Transl Psychiatry. 2015 Apr 21;5(4):e552. doi: 10.1038/tp.2015.42.
• [15] PRAS40 alleviates neurotoxic prion peptide-induced apoptosis via mTOR-AKT signaling.CNS Neurosci Ther. 2017 May;23(5):416-427. doi: 10.1111/cns.12685. Epub 2017 Mar 14.
• [16] Overexpression of BAT3 alleviates prion protein fragment PrP106-126-induced neuronal apoptosis.CNS Neurosci Ther. 2014 Aug;20(8):737-47. doi: 10.1111/cns.12243. Epub 2014 Mar 15.
• [17] Genetic variability of the gene cluster CALHM 1-3 in sporadic Creutzfeldt-Jakob disease.Prion. 2012 Sep-Oct;6(4):407-12. doi: 10.4161/pri.20785. Epub 2012 Aug 9.
• [18] Parkin Overexpression Ameliorates PrP106-126-Induced Neurotoxicity via Enhanced Autophagy in N2a Cells.Cell Mol Neurobiol. 2017 May;37(4):717-728. doi: 10.1007/s10571-016-0407-7. Epub 2016 Jul 18.
• [19] Gene expression profiling on sheep brain reveals differential transcripts in scrapie-affected/not-affected animals.Brain Res. 2007 Apr 20;1142:217-22. doi: 10.1016/j.brainres.2007.01.033. Epub 2007 Jan 17.
• [20] A Copine family member, Cpne8, is a candidate quantitative trait gene for prion disease incubation time in mouse.Neurogenetics. 2010 May;11(2):185-91. doi: 10.1007/s10048-009-0219-8. Epub 2009 Oct 1.
• [21] Cystatin F is a biomarker of prion pathogenesis in mice.PLoS One. 2017 Feb 8;12(2):e0171923. doi: 10.1371/journal.pone.0171923. eCollection 2017.
• [22] Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in mice.Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13722-7. doi: 10.1073/pnas.1208917109. Epub 2012 Aug 6.
• [23] Rational Structure-Based Design of Fluorescent Probes for Amyloid Folds.Chembiochem. 2019 May 2;20(9):1161-1166. doi: 10.1002/cbic.201800664. Epub 2019 Mar 7.
• [24] Biological network inferences for a protection mechanism against familial Creutzfeldt-Jakob disease with E200K pathogenic mutation.BMC Med Genomics. 2014 Aug 22;7:52. doi: 10.1186/1755-8794-7-52.
• [25] Muskelin Coordinates PrP(C) Lysosome versus Exosome Targeting and Impacts Prion Disease Progression.Neuron. 2018 Sep 19;99(6):1155-1169.e9. doi: 10.1016/j.neuron.2018.08.010. Epub 2018 Aug 30.
• [26] Cerebrospinal fluid neurofilament light in suspected sporadic Creutzfeldt-Jakob disease.J Clin Neurosci. 2019 Feb;60:124-127. doi: 10.1016/j.jocn.2018.09.031. Epub 2018 Oct 9.
• [27] Proteomic Screen of Brain Glycoproteome Reveals Prion Specific Marker of Pathogenesis.Proteomics. 2018 Jan;18(1). doi: 10.1002/pmic.201700296.
• [28] Protein Misfolding, Signaling Abnormalities and Altered Fast Axonal Transport: Implications for Alzheimer and Prion Diseases.Front Cell Neurosci. 2019 Jul 30;13:350. doi: 10.3389/fncel.2019.00350. eCollection 2019.
• [29] Variants of PLCXD3 are not associated with variant or sporadic Creutzfeldt-Jakob disease in a large international study.BMC Med Genet. 2016 Apr 7;17:28. doi: 10.1186/s12881-016-0278-2.
• [30] Overexpression of PLK3 Mediates the Degradation of Abnormal Prion Proteins Dependent on Chaperone-Mediated Autophagy.Mol Neurobiol. 2017 Aug;54(6):4401-4413. doi: 10.1007/s12035-016-9985-0. Epub 2016 Jun 25.
• [31] First report of polymorphisms in the prion-like protein gene (PRND): implications for human prion diseases.Neurosci Lett. 2000 Jun 2;286(2):144-8. doi: 10.1016/s0304-3940(00)01100-9.
• [32] SARM1 deficiency up-regulates XAF1, promotes neuronal apoptosis, and accelerates prion disease.J Exp Med. 2019 Apr 1;216(4):743-756. doi: 10.1084/jem.20171885. Epub 2019 Mar 6.
• [33] Impaired transport of intrinsically disordered proteins through the Sec61 and SecY translocon; implications for prion diseases.Prion. 2018 Mar 4;12(2):88-92. doi: 10.1080/19336896.2018.1435936. Epub 2018 Mar 29.
• [34] Differential overexpression of SERPINA3 in human prion diseases.Sci Rep. 2017 Nov 15;7(1):15637. doi: 10.1038/s41598-017-15778-8.
• [35] The genetics of disorders with synuclein pathology and parkinsonism.Hum Mol Genet. 1999;8(10):1901-5. doi: 10.1093/hmg/8.10.1901.
• [36] Biological properties of the PrP-like Shadoo protein.Front Biosci (Landmark Ed). 2011 Jan 1;16(4):1505-16. doi: 10.2741/3801.
• [37] Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study.Lancet Neurol. 2009 Jan;8(1):57-66. doi: 10.1016/S1474-4422(08)70265-5.
• [38] Molecular interaction of TPPP with PrP antagonized the CytoPrP-induced disruption of microtubule structures and cytotoxicity.PLoS One. 2011;6(8):e23079. doi: 10.1371/journal.pone.0023079. Epub 2011 Aug 12.