Entry
Name
Prion disease - Microcebus murinus (gray mouse lemur)
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
BRITE hierarchy
Pathway map
Ortholog table
Organism
Microcebus murinus (gray mouse lemur) [GN:
mmur ]
Gene
105882598 GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209 ]
105865636 GRIN2D; glutamate receptor ionotropic, NMDA 2D isoform X1 [KO:K05212 ]
105882232 CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849 ]
105861596 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
105875072 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
105856433 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853 ]
105859992 CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
105880242 EIF2S1; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 2 subunit 1 [KO:K03237 ]
105858535 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
105869384 ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
105857276 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959 ]
105868798 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105863295 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105857150 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105869973 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
105866328 VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040 ]
105878143 VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041 ]
105860911 NDUFV2; LOW QUALITY PROTEIN: NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial [KO:K03943 ] [EC:7.1.1.2 ]
105879121 NDUFV3; NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial isoform X5 [KO:K03944 ]
109729268 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1-like [KO:K03945 ]
109730235 NDUFA1; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 [KO:K03945 ]
109731114 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1-like [KO:K03945 ]
105879883 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 [KO:K03945 ]
105862566 NDUFA2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 isoform X1 [KO:K03946 ]
105874716 NDUFA3; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 [KO:K03947 ]
105877970 NDUFA4L2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 isoform X1 [KO:K03948 ]
105864152 NDUFA5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 [KO:K03949 ]
105858589 NDUFA6; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 [KO:K03950 ]
105885663 NDUFA7; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 [KO:K03951 ]
105875144 NDUFA8; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 [KO:K03952 ]
105881452 NDUFA9; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial [KO:K03953 ]
105866363 NDUFA10; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial [KO:K03954 ]
105869653 NDUFA11; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 [KO:K03956 ]
105877076 NDUFA12; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 [KO:K11352 ]
105858346 NDUFA13; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 [KO:K11353 ]
105873243 NDUFB2; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial [KO:K03958 ]
105856967 NDUFB3; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 [KO:K03959 ]
105879910 NDUFB4; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 [KO:K03960 ]
105855817 NDUFB5; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial [KO:K03961 ]
105871186 NDUFB6; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 [KO:K03962 ]
105867920 NDUFB7; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 [KO:K03963 ]
105873650 NDUFB8; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial isoform X1 [KO:K03964 ]
105884392 NDUFB9; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 isoform X1 [KO:K03965 ]
105862787 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9-like [KO:K03965 ]
105859618 NDUFB10; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 [KO:K03966 ]
105862994 NDUFB11; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial [KO:K11351 ]
105873549 NDUFS2; NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial [KO:K03935 ] [EC:7.1.1.2 ]
105884600 NDUFS3; NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial [KO:K03936 ] [EC:7.1.1.2 ]
105867019 NDUFS4; NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial isoform X1 [KO:K03937 ]
105881169 NADH dehydrogenase [ubiquinone] iron-sulfur protein 5-like [KO:K03938 ]
105879547 NDUFS5; NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 [KO:K03938 ]
105876445 NDUFS6; NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial [KO:K03939 ]
105860789 NDUFS7; NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial isoform X1 [KO:K03940 ] [EC:7.1.1.2 ]
105867432 NDUFS8; NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial isoform X1 [KO:K03941 ] [EC:7.1.1.2 ]
109730487 NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial-like [KO:K03967 ]
105872357 NDUFC1; NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial [KO:K03967 ]
105876466 SDHA; succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform X1 [KO:K00234 ] [EC:1.3.5.1 ]
105870472 SDHB; succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial [KO:K00235 ] [EC:1.3.5.1 ]
105882171 succinate dehydrogenase cytochrome b560 subunit, mitochondrial [KO:K00236 ]
105873557 SDHC; succinate dehydrogenase cytochrome b560 subunit, mitochondrial [KO:K00236 ]
105862943 SDHD; succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial isoform X1 [KO:K00237 ]
105863187 succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial [KO:K00237 ]
105877497 cytochrome b-c1 complex subunit 6, mitochondrial isoform X1 [KO:K00416 ]
105871362 cytochrome c oxidase subunit 4 isoform 1, mitochondrial [KO:K02263 ]
105866063 cytochrome c oxidase subunit 4 isoform 2, mitochondrial [KO:K02263 ]
105859388 cytochrome c oxidase subunit 7A2, mitochondrial isoform X1 [KO:K02270 ]
105866963 cytochrome c oxidase subunit 7A-related protein, mitochondrial [KO:K02270 ]
105874841 LOW QUALITY PROTEIN: ATP synthase subunit alpha, mitochondrial-like [KO:K02132 ]
105885383 ATP5A1; LOW QUALITY PROTEIN: ATP synthase subunit alpha, mitochondrial [KO:K02132 ]
105863924 ATP synthase subunit gamma, mitochondrial-like isoform X1 [KO:K02136 ]
105858234 ATP5C1; LOW QUALITY PROTEIN: ATP synthase subunit gamma, mitochondrial [KO:K02136 ]
105864015 ATP5F1; ATP synthase F(0) complex subunit B1, mitochondrial isoform X1 [KO:K02127 ]
105885081 ATP5G1; ATP synthase F(0) complex subunit C1, mitochondrial [KO:K02128 ]
105870975 ATP5G2; ATP synthase F(0) complex subunit C2, mitochondrial isoform X1 [KO:K02128 ]
105865079 ATP5G3; ATP synthase F(0) complex subunit C3, mitochondrial [KO:K02128 ]
105855762 PSMD2; 26S proteasome non-ATPase regulatory subunit 2 [KO:K03028 ]
105862831 PSMD1; 26S proteasome non-ATPase regulatory subunit 1 [KO:K03032 ]
105872092 PSMD3; 26S proteasome non-ATPase regulatory subunit 3 [KO:K03033 ]
105880905 PSMD9; 26S proteasome non-ATPase regulatory subunit 9 [KO:K06693 ]
105861630 PSMD12; LOW QUALITY PROTEIN: 26S proteasome non-ATPase regulatory subunit 12 [KO:K03035 ]
105855223 PSMD11; 26S proteasome non-ATPase regulatory subunit 11 [KO:K03036 ]
105858950 PSMD7; 26S proteasome non-ATPase regulatory subunit 7 [KO:K03038 ]
105874077 PSMD13; 26S proteasome non-ATPase regulatory subunit 13 [KO:K03039 ]
105873023 PSMD4; 26S proteasome non-ATPase regulatory subunit 4 isoform X1 [KO:K03029 ]
105855038 PSMD14; 26S proteasome non-ATPase regulatory subunit 14 [KO:K03030 ]
105876832 PSMD8; 26S proteasome non-ATPase regulatory subunit 8 [KO:K03031 ]
105875718 ADRM1; proteasomal ubiquitin receptor ADRM1 isoform X1 [KO:K06691 ]
105854849 LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283 ]
105862660 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
105855821 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
105886063 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
105881219 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
105855026 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
105877483 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
105868254 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
105883746 RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860 ]
105864304 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
105865052 ATF2; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
105873936 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
105874305 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
105885209 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
105885942 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
105859108 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
105855129 cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
105858143 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
Compound
Reference
Authors
Saa P, Harris DA, Cervenakova L
Title
Mechanisms of prion-induced neurodegeneration.
Journal
Reference
Authors
Goold R, McKinnon C, Tabrizi SJ
Title
Prion degradation pathways: Potential for therapeutic intervention.
Journal
Reference
Authors
Soto C, Satani N
Title
The intricate mechanisms of neurodegeneration in prion diseases.
Journal
Reference
Authors
Mays CE, Soto C
Title
The stress of prion disease.
Journal
Reference
Authors
Jones E, Mead S
Title
Genetic risk factors for Creutzfeldt-Jakob disease.
Journal
Reference
Authors
Kovacs GG, Budka H
Title
Prion diseases: from protein to cell pathology.
Journal
Reference
Authors
Campana V, Sarnataro D, Zurzolo C
Title
The highways and byways of prion protein trafficking.
Journal
Reference
Authors
Caughey B, Baron GS
Title
Prions and their partners in crime.
Journal
Reference
Authors
Chiesa R, Harris DA
Title
Prion diseases: what is the neurotoxic molecule?
Journal
Reference
Authors
Fasano C, Campana V, Zurzolo C
Title
Prions: protein only or something more? Overview of potential prion cofactors.
Journal
Reference
Authors
Roucou X, Gains M, LeBlanc AC
Title
Neuroprotective functions of prion protein.
Journal
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
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
Reference
Authors
Ryskalin L, Busceti CL, Biagioni F, Limanaqi F, Familiari P, Frati A, Fornai F
Title
Prion Protein in Glioblastoma Multiforme.
Journal
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
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
Reference
Authors
Song Z, Zhao D, Yang L
Title
Molecular mechanisms of neurodegeneration mediated by dysfunctional subcellular organelles in transmissible spongiform encephalopathies.
Journal
Reference
Authors
Halliday M, Hughes D, Mallucci GR
Title
Fine-tuning PERK signaling for neuroprotection.
Journal
Reference
Authors
Hughes D, Halliday M
Title
What Is Our Current Understanding of PrP(Sc)-Associated Neurotoxicity and Its Molecular Underpinnings?
Journal
Reference
Authors
Hetz C, Mollereau B
Title
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases.
Journal
Reference
Authors
Hughes D, Mallucci GR
Title
The unfolded protein response in neurodegenerative disorders - therapeutic modulation of the PERK pathway.
Journal
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
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
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
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
Reference
Authors
Ciechanover A, Kwon YT
Title
Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies.
Journal
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
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
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
Reference
Authors
Zamponi E, Pigino GF
Title
Protein Misfolding, Signaling Abnormalities and Altered Fast Axonal Transport: Implications for Alzheimer and Prion Diseases.
Journal
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
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
Reference
Authors
Didonna A
Title
Prion protein and its role in signal transduction.
Journal
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
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
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
Reference
Authors
Dearmond SJ, Bajsarowicz K
Title
PrPSc accumulation in neuronal plasma membranes links Notch-1 activation to dendritic degeneration in prion diseases.
Journal
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
Reference
Authors
Aguzzi A, Zhu C
Title
Microglia in prion diseases.
Journal
Reference
Authors
Mabbott NA
Title
The complement system in prion diseases.
Journal
Reference
Authors
Mallucci G, Collinge J
Title
Rational targeting for prion therapeutics.
Journal
Related pathway
mmur04141 Protein processing in endoplasmic reticulum
mmur04610 Complement and coagulation cascades
KO pathway
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