PATHWAY: ssc05016 Help
Entry
Name
Huntington disease - Sus scrofa (pig)
Description
Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality changes and dementia. HD is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine (polyQ) close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. Full-length huntingtin is cleaved by proteases in the cytoplasm, leading to the formation of cytoplasmic and neuritic aggregates. mHtt also alters vesicular transport and recycling, causes cytosolic and mitochondrial Ca2+ overload, triggers endoplasmic reticulum stress through proteasomal dysfunction, and impairs autophagy function, increasing neuronal death susceptibility. N-terminal fragments containing the polyQ strech translocate to the nucleus where they impair transcription and induce neuronal death.
Class
Human Diseases; Neurodegenerative disease
BRITE hierarchy
Pathway map
Ortholog table
Organism
Sus scrofa (pig) [GN:
ssc ]
Gene
100523598 HIP1; LOW QUALITY PROTEIN: huntingtin-interacting protein 1 [KO:K04559 ]
100511777 DNAH2; LOW QUALITY PROTEIN: dynein heavy chain 2, axonemal [KO:K10408 ]
100157866 DNAH7; LOW QUALITY PROTEIN: dynein heavy chain 7, axonemal [KO:K10408 ]
100156478 DNAH8; LOW QUALITY PROTEIN: dynein heavy chain 8, axonemal [KO:K10408 ]
100623921 DNAH5; LOW QUALITY PROTEIN: dynein heavy chain 5, axonemal [KO:K10408 ]
100738073 DNAH3; LOW QUALITY PROTEIN: dynein heavy chain 3, axonemal [KO:K10408 ]
102163805 DNAH17; LOW QUALITY PROTEIN: dynein heavy chain 17, axonemal [KO:K10408 ]
100623248 DNALI1; LOW QUALITY PROTEIN: axonemal dynein light intermediate polypeptide 1 [KO:K10410 ]
100624095 DNAI2; dynein intermediate chain 2, axonemal isoform X1 [KO:K11143 ]
654405 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
100152679 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100157641 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100516581 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100525148 PLCB3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858 ] [EC:3.1.4.11 ]
102164336 CACNA1B; LOW QUALITY PROTEIN: voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849 ]
397440 GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208 ]
397454 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
100516047 SLC1A3; excitatory amino acid transporter 1 isoform 1 [KO:K05614 ]
100627068 SLC1A2; excitatory amino acid transporter 2 isoform X2 [KO:K05613 ]
100627780 KCNJ10; ATP-sensitive inward rectifier potassium channel 10 [KO:K05003 ]
100737579 POLR2D; DNA-directed RNA polymerase II subunit RPB4 isoform X1 [KO:K03012 ]
100623333 POLR2E; DNA-directed RNA polymerases I, II, and III subunit RPABC1 [KO:K03013 ]
100737214 POLR2F; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014 ]
100628241 POLR2H; DNA-directed RNA polymerases I, II, and III subunit RPABC3 [KO:K03016 ]
414403 POLR2I; DNA-directed RNA polymerase II subunit RPB9 isoform 1 [KO:K03017 ]
100511241 POLR2L; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007 ]
100156985 DNA-directed RNA polymerases I, II, and III subunit RPABC5-like [KO:K03007 ]
100521614 POLR2J; DNA-directed RNA polymerase II subunit RPB11-a [KO:K03008 ]
100524560 POLR2K; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009 ]
397495 BDNF; brain-derived neurotrophic factor precursor [KO:K04355 ]
100037274 TAF4B; transcription initiation factor TFIID subunit 4B [KO:K03129 ]
100626452 TAF4; LOW QUALITY PROTEIN: transcription initiation factor TFIID subunit 4 [KO:K03129 ]
100154426 TBPL2; TATA box-binding protein-like protein 2 isoform X6 [KO:K03120 ]
100736562 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
100142688 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
100142689 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
100516663 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
100520468 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
100522979 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
100515635 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
397013 PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha [KO:K07202 ]
397671 PPARG; peroxisome proliferator-activated receptor gamma [KO:K08530 ]
397279 TFAM; transcription factor A, mitochondrial precursor [KO:K11830 ]
100620809 NDUFV3; NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial isoform X1 [KO:K03944 ]
100515069 NDUFA1; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 [KO:K03945 ]
100520950 NDUFA2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 [KO:K03946 ]
100520312 NDUFA3; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 isoform X2 [KO:K03947 ]
100156288 NDUFA4L2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 [KO:K03948 ]
100525371 NDUFA5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 isoform X1 [KO:K03949 ]
100157442 NDUFA6; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 [KO:K03950 ]
100517634 NDUFA7; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 [KO:K03951 ]
100154443 NDUFA8; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 [KO:K03952 ]
100524622 NDUFA9; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial [KO:K03953 ]
100521478 NDUFA10; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial [KO:K03954 ]
100514033 NDUFA11; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 [KO:K03956 ]
100518016 NDUFA12; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 [KO:K11352 ]
100622110 NDUFA13; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 [KO:K11353 ]
100739619 NDUFB1; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 [KO:K03957 ]
100513895 NDUFB2; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial [KO:K03958 ]
100525083 NDUFB3; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 isoform X2 [KO:K03959 ]
100624335 NDUFB4; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 [KO:K03960 ]
100523751 NDUFB5; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial isoform X1 [KO:K03961 ]
733605 NDUFB6; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 [KO:K03962 ]
100737726 NDUFB7; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 [KO:K03963 ]
448979 NDUFB8; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial [KO:K03964 ]
100154130 NDUFB9; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 [KO:K03965 ]
100623873 NDUFB10; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 [KO:K03966 ]
100522775 NDUFB11; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial isoform X2 [KO:K11351 ]
100156075 NDUFS2; NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform X1 [KO:K03935 ] [EC:7.1.1.2 ]
100510948 NDUFS3; NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial [KO:K03936 ] [EC:7.1.1.2 ]
100516161 NDUFS4; NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial isoform X1 [KO:K03937 ]
100514655 NDUFS5; NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 [KO:K03938 ]
100520115 NDUFS6; NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial [KO:K03939 ]
100624738 NDUFS7; NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial isoform X3 [KO:K03940 ] [EC:7.1.1.2 ]
100521945 NDUFS8; NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial isoform X1 [KO:K03941 ] [EC:7.1.1.2 ]
100037985 NDUFC1; NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial [KO:K03967 ]
780433 SDHA; succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform X1 [KO:K00234 ] [EC:1.3.5.1 ]
414412 SDHB; succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial precursor [KO:K00235 ] [EC:1.3.5.1 ]
100524676 SDHC; succinate dehydrogenase cytochrome b560 subunit, mitochondrial [KO:K00236 ]
100048954 SDHD; succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial [KO:K00237 ]
100156879 cytochrome b-c1 complex subunit 1, mitochondrial isoform X4 [KO:K00414 ]
100524873 cytochrome b-c1 complex subunit 6, mitochondrial isoform X1 [KO:K00416 ]
100157621 UQCRB; ubiquinol-cytochrome c reductase binding protein [KO:K00417 ]
100624067 cytochrome c oxidase subunit 4 isoform 1, mitochondrial [KO:K02263 ]
110257420 cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform X1 [KO:K02263 ]
492822 COX5B; cytochrome c oxidase subunit 5B, mitochondrial precursor [KO:K02265 ]
100152232 COX6A1; cytochrome c oxidase subunit VIa polypeptide 1 [KO:K02266 ]
399685 COX7A1; cytochrome c oxidase subunit 7A1, mitochondrial precursor [KO:K02270 ]
100038000 COX7A2; cytochrome c oxidase subunit 7A2, mitochondrial [KO:K02270 ]
100516606 cytochrome c oxidase subunit 7A-related protein, mitochondrial isoform X4 [KO:K02270 ]
100037990 COX7C; cytochrome c oxidase subunit 7C, mitochondrial precursor [KO:K02272 ]
102160861 ATP5C1; ATP synthase subunit gamma, mitochondrial isoform X1 [KO:K02136 ]
100154817 ATP5F1; ATP synthase F(0) complex subunit B1, mitochondrial [KO:K02127 ]
574054 ATP5G1; ATP synthase F(0) complex subunit C1, mitochondrial [KO:K02128 ]
100513629 ATP5G3; ATP synthase F(0) complex subunit C3, mitochondrial [KO:K02128 ]
100037988 ATP5G2; ATP synthase F(0) complex subunit C2, mitochondrial isoform X1 [KO:K02128 ]
100519871 ATP synthase F(0) complex subunit C1, mitochondrial-like [KO:K02128 ]
733678 ATP5O; ATP synthase subunit O, mitochondrial precursor [KO:K02137 ]
397010 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
397659 VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040 ]
397651 VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041 ]
100513283 APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084 ]
100627568 PSMD2; 26S proteasome non-ATPase regulatory subunit 2 [KO:K03028 ]
100153828 PSMD1; 26S proteasome non-ATPase regulatory subunit 1 [KO:K03032 ]
100512253 PSMD3; 26S proteasome non-ATPase regulatory subunit 3 [KO:K03033 ]
100525255 PSMD9; 26S proteasome non-ATPase regulatory subunit 9 [KO:K06693 ]
100524394 PSMD12; 26S proteasome non-ATPase regulatory subunit 12 [KO:K03035 ]
100523278 PSMD11; LOW QUALITY PROTEIN: 26S proteasome non-ATPase regulatory subunit 11 [KO:K03036 ]
100519870 PSMD6; 26S proteasome non-ATPase regulatory subunit 6 [KO:K03037 ]
100626274 PSMD7; 26S proteasome non-ATPase regulatory subunit 7 [KO:K03038 ]
100517815 PSMD13; 26S proteasome non-ATPase regulatory subunit 13 [KO:K03039 ]
733583 PSMD4; 26S proteasome non-ATPase regulatory subunit 4 [KO:K03029 ]
100156327 PSMD14; 26S proteasome non-ATPase regulatory subunit 14 [KO:K03030 ]
100515483 PSMD8; 26S proteasome non-ATPase regulatory subunit 8 [KO:K03031 ]
110257483 ADRM1; proteasomal ubiquitin receptor ADRM1 isoform X1 [KO:K06691 ]
100622699 RB1CC1; RB1-inducible coiled-coil protein 1 isoform X1 [KO:K17589 ]
100519700 AMBRA1; activating molecule in BECN1-regulated autophagy protein 1 isoform X3 [KO:K17985 ]
100155666 ATG14; beclin 1-associated autophagy-related key regulator [KO:K17889 ]
100462758 WIPI1; WD repeat domain phosphoinositide-interacting protein 1 [KO:K17908 ]
100462759 WIPI2; WD repeat domain phosphoinositide-interacting protein 2 [KO:K17908 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C04549 1-Phosphatidyl-1D-myo-inositol 3-phosphate
Reference
Authors
Landles C, Bates GP
Title
Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review series.
Journal
Reference
Authors
Borrell-Pages M, Zala D, Humbert S, Saudou F
Title
Huntington's disease: from huntingtin function and dysfunction to therapeutic strategies.
Journal
Reference
Authors
Bossy-Wetzel E, Petrilli A, Knott AB
Title
Mutant huntingtin and mitochondrial dysfunction.
Journal
Reference
Authors
Cattaneo E, Zuccato C, Tartari M
Title
Normal huntingtin function: an alternative approach to Huntington's disease.
Journal
Reference
Authors
Bezprozvanny I, Hayden MR
Title
Deranged neuronal calcium signaling and Huntington disease.
Journal
Reference
Authors
Sawa A, Tomoda T, Bae BI
Title
Mechanisms of neuronal cell death in Huntington's disease.
Journal
Reference
Authors
Ross CA.
Title
Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disorders.
Journal
Reference
Authors
Ross CA
Title
Huntington's disease: new paths to pathogenesis.
Journal
Reference
Authors
Coffey ET
Title
Nuclear and cytosolic JNK signalling in neurons.
Journal
Reference
Authors
Morfini GA, You YM, Pollema SL, Kaminska A, Liu K, Yoshioka K, Bjorkblom B, Coffey ET, Bagnato C, Han D, Huang CF, Banker G, Pigino G, Brady ST
Title
Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin.
Journal
Reference
Authors
Kumar P, Kumar D, Jha SK, Jha NK, Ambasta RK
Title
Ion Channels in Neurological Disorders.
Journal
Reference
Authors
Proft J, Weiss N
Title
Rectifying rectifier channels in Huntington disease.
Journal
Reference
Authors
Tang TS, Slow E, Lupu V, Stavrovskaya IG, Sugimori M, Llinas R, Kristal BS, Hayden MR, Bezprozvanny I
Title
Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease.
Journal
Reference
Authors
Mackay JP, Nassrallah WB, Raymond LA
Title
Cause or compensation?-Altered neuronal Ca(2+) handling in Huntington's disease.
Journal
Reference
Authors
Mattson MP.
Title
Accomplices to neuronal death.
Journal
Reference
Authors
McGill JK, Beal MF
Title
PGC-1alpha, a new therapeutic target in Huntington's disease?
Journal
Reference
Authors
Intihar TA, Martinez EA, Gomez-Pastor R
Title
Mitochondrial Dysfunction in Huntington's Disease; Interplay Between HSF1, p53 and PGC-1alpha Transcription Factors.
Journal
Reference
Authors
La Spada AR, Morrison RS
Title
The power of the dark side: Huntington's disease protein and p53 form a deadly alliance.
Journal
Reference
Authors
Lesort M, Chun W, Tucholski J, Johnson GV
Title
Does tissue transglutaminase play a role in Huntington's disease?
Journal
Reference
Authors
Bae BI, Xu H, Igarashi S, Fujimuro M, Agrawal N, Taya Y, Hayward SD, Moran TH, Montell C, Ross CA, Snyder SH, Sawa A
Title
p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease.
Journal
Reference
Authors
Li SH, Cheng AL, Zhou H, Lam S, Rao M, Li H, Li XJ
Title
Interaction of Huntington disease protein with transcriptional activator Sp1.
Journal
Reference
Authors
Vidal RL, Matus S, Bargsted L, Hetz C
Title
Targeting autophagy in neurodegenerative diseases.
Journal
Reference
Authors
Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, MacDonald M, Yankner B, Yuan J
Title
Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1.
Journal
Related pathway
ssc04141 Protein processing in endoplasmic reticulum
KO pathway