PATHWAY: mmu05016 Help
Entry
Name
Huntington disease - Mus musculus (house mouse)
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
Disease
Organism
Mus musculus (house mouse) [GN:
mmu ]
Gene
102634451 Ndufab1-ps; NADH:ubiquinone oxidoreductase subunit AB1b [KO:K03955 ]
104130 Ndufb11; NADH:ubiquinone oxidoreductase subunit B11 [KO:K11351 ]
110323 Cox6b1; cytochrome c oxidase, subunit 6B1 [KO:K02267 ]
11739 Slc25a4; solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 4 [KO:K05863 ]
11740 Slc25a5; solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 5 [KO:K05863 ]
11771 Ap2a1; adaptor-related protein complex 2, alpha 1 subunit [KO:K11824 ]
11772 Ap2a2; adaptor-related protein complex 2, alpha 2 subunit [KO:K11824 ]
11773 Ap2m1; adaptor-related protein complex 2, mu 1 subunit [KO:K11826 ]
11783 Apaf1; apoptotic peptidase activating factor 1 [KO:K02084 ]
11946 Atp5f1a; ATP synthase F1 subunit alpha [KO:K02132 ]
11949 Atp5f1c; ATP synthase F1 subunit gamma [KO:K02136 ]
11950 Atp5pb; ATP synthase peripheral stalk-membrane subunit b [KO:K02127 ]
11951 Atp5mc1; ATP synthase membrane subunit c locus 1 [KO:K02128 ]
11957 Atp5pf; ATP synthase peripheral stalk subunit F6 [KO:K02131 ]
12064 Bdnf; brain derived neurotrophic factor [KO:K04355 ]
12287 Cacna1b; calcium channel, voltage-dependent, N type, alpha 1B subunit [KO:K04849 ]
12857 Cox4i1; cytochrome c oxidase subunit 4I1 [KO:K02263 ]
12858 Cox5a; cytochrome c oxidase subunit 5A [KO:K02264 ]
12859 Cox5b; cytochrome c oxidase subunit 5B [KO:K02265 ]
12861 Cox6a1; cytochrome c oxidase subunit 6A1 [KO:K02266 ]
12862 Cox6a2; cytochrome c oxidase subunit 6A2 [KO:K02266 ]
12864 Cox6c; cytochrome c oxidase subunit 6C [KO:K02268 ]
12865 Cox7a1; cytochrome c oxidase subunit 7A1 [KO:K02270 ]
12866 Cox7a2; cytochrome c oxidase subunit 7A2 [KO:K02270 ]
12867 Cox7c; cytochrome c oxidase subunit 7C [KO:K02272 ]
12868 Cox8a; cytochrome c oxidase subunit 8A [KO:K02273 ]
12869 Cox8b; cytochrome c oxidase subunit 8B [KO:K02273 ]
12912 Creb1; cAMP responsive element binding protein 1 [KO:K05870 ]
12913 Creb3; cAMP responsive element binding protein 3 [KO:K09048 ]
13385 Dlg4; discs large MAGUK scaffold protein 4 [KO:K11828 ]
13411 Dnah11; dynein, axonemal, heavy chain 11 [KO:K10408 ]
13417 Dnah8; dynein, axonemal, heavy chain 8 [KO:K10408 ]
14682 Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634 ]
14799 Gria1; glutamate receptor, ionotropic, AMPA1 (alpha 1) [KO:K05197 ]
14800 Gria2; glutamate receptor, ionotropic, AMPA2 (alpha 2) [KO:K05198 ]
14802 Gria4; glutamate receptor, ionotropic, AMPA4 (alpha 4) [KO:K05200 ]
14810 Grin1; glutamate receptor, ionotropic, NMDA1 (zeta 1) [KO:K05208 ]
14812 Grin2b; glutamate receptor, ionotropic, NMDA2B (epsilon 2) [KO:K05210 ]
15114 Hap1; huntingtin-associated protein 1 [KO:K04647 ]
16438 Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958 ]
16513 Kcnj10; potassium inwardly-rectifying channel, subfamily J, member 10 [KO:K05003 ]
17463 Psmd7; proteasome (prosome, macropain) 26S subunit, non-ATPase, 7 [KO:K03038 ]
17709 COX2; cytochrome c oxidase subunit II [KO:K02261 ]
17710 COX3; cytochrome c oxidase subunit III [KO:K02262 ]
17749 Polr2k; polymerase (RNA) II (DNA directed) polypeptide K [KO:K03009 ]
17991 Ndufa2; NADH:ubiquinone oxidoreductase subunit A2 [KO:K03946 ]
17992 Ndufa4; Ndufa4, mitochondrial complex associated [KO:K03948 ]
17993 Ndufs4; NADH:ubiquinone oxidoreductase core subunit S4 [KO:K03937 ]
19016 Pparg; peroxisome proliferator activated receptor gamma [KO:K08530 ]
19017 Ppargc1a; peroxisome proliferative activated receptor, gamma, coactivator 1 alpha [KO:K07202 ]
19179 Psmc1; protease (prosome, macropain) 26S subunit, ATPase 1 [KO:K03062 ]
19181 Psmc2; proteasome (prosome, macropain) 26S subunit, ATPase 2 [KO:K03061 ]
19182 Psmc3; proteasome (prosome, macropain) 26S subunit, ATPase 3 [KO:K03065 ]
19184 Psmc5; protease (prosome, macropain) 26S subunit, ATPase 5 [KO:K03066 ]
19185 Psmd4; proteasome (prosome, macropain) 26S subunit, non-ATPase, 4 [KO:K03029 ]
19712 Rest; RE1-silencing transcription factor [KO:K09222 ]
20021 Polr2c; polymerase (RNA) II (DNA directed) polypeptide C [KO:K03011 ]
20022 Polr2j; polymerase (RNA) II (DNA directed) polypeptide J [KO:K03008 ]
20422 Sem1; SEM1, 26S proteasome complex subunit [KO:K10881 ]
20463 Cox7a2l; cytochrome c oxidase subunit 7A2 like [KO:K02270 ]
20466 Sin3a; transcriptional regulator, SIN3A (yeast) [KO:K11644 ]
20511 Slc1a2; solute carrier family 1 (glial high affinity glutamate transporter), member 2 [KO:K05613 ]
20512 Slc1a3; solute carrier family 1 (glial high affinity glutamate transporter), member 3 [KO:K05614 ]
20683 Sp1; trans-acting transcription factor 1 [KO:K04684 ]
208647 Creb3l2; cAMP responsive element binding protein 3-like 2 [KO:K09048 ]
208677 Creb3l3; cAMP responsive element binding protein 3-like 3 [KO:K09048 ]
21762 Psmd2; proteasome (prosome, macropain) 26S subunit, non-ATPase, 2 [KO:K03028 ]
21780 Tfam; transcription factor A, mitochondrial [KO:K11830 ]
22059 Trp53; transformation related protein 53 [KO:K04451 ]
22123 Psmd3; proteasome (prosome, macropain) 26S subunit, non-ATPase, 3 [KO:K03033 ]
22227 Ucp1; uncoupling protein 1 (mitochondrial, proton carrier) [KO:K08769 ]
22272 Uqcrq; ubiquinol-cytochrome c reductase, complex III subunit VII [KO:K00418 ]
22273 Uqcrc1; ubiquinol-cytochrome c reductase core protein 1 [KO:K00414 ]
22333 Vdac1; voltage-dependent anion channel 1 [KO:K05862 ]
22334 Vdac2; voltage-dependent anion channel 2 [KO:K15040 ]
22335 Vdac3; voltage-dependent anion channel 3 [KO:K15041 ]
226977 Actr1b; ARP1 actin-related protein 1B, centractin beta [KO:K16575 ]
228033 Atp5mc3; ATP synthase membrane subunit c locus 3 [KO:K02128 ]
228980 Taf4; TATA-box binding protein associated factor 4 [KO:K03129 ]
230075 Ndufb6; NADH:ubiquinone oxidoreductase subunit B6 [KO:K03962 ]
231991 Creb5; cAMP responsive element binding protein 5 [KO:K09047 ]
232910 Ap2s1; adaptor-related protein complex 2, sigma 1 subunit [KO:K11827 ]
23996 Psmc4; proteasome (prosome, macropain) 26S subunit, ATPase, 4 [KO:K03063 ]
23997 Psmd13; proteasome (prosome, macropain) 26S subunit, non-ATPase, 13 [KO:K03039 ]
245841 Polr2h; polymerase (RNA) II (DNA directed) polypeptide H [KO:K03016 ]
26427 Creb3l1; cAMP responsive element binding protein 3-like 1 [KO:K09048 ]
28080 Atp5po; ATP synthase peripheral stalk subunit OSCP [KO:K02137 ]
407785 Ndufs6; NADH:ubiquinone oxidoreductase core subunit S6 [KO:K03939 ]
407790 Ndufa4l2; Ndufa4, mitochondrial complex associated like 2 [KO:K03948 ]
432611 Dnai2; dynein axonemal intermediate chain 2 [KO:K11143 ]
52639 Wipi1; WD repeat domain, phosphoinositide interacting 1 [KO:K17908 ]
53623 Gria3; glutamate receptor, ionotropic, AMPA3 (alpha 3) [KO:K05199 ]
54130 Actr1a; ARP1 actin-related protein 1A, centractin alpha [KO:K16575 ]
54152 Dnal4; dynein, axonemal, light chain 4 [KO:K10412 ]
54405 Ndufa1; NADH:ubiquinone oxidoreductase subunit A1 [KO:K03945 ]
56087 Dnah10; dynein, axonemal, heavy chain 10 [KO:K10408 ]
56436 Adrm1; adhesion regulating molecule 1 26S proteasome ubiquitin receptor [KO:K06691 ]
56444 Actr10; ARP10 actin-related protein 10 [KO:K16576 ]
57296 Psmd8; proteasome (prosome, macropain) 26S subunit, non-ATPase, 8 [KO:K03031 ]
59029 Psmd14; proteasome (prosome, macropain) 26S subunit, non-ATPase, 14 [KO:K03030 ]
595136 Ndufs5; NADH:ubiquinone oxidoreductase core subunit S5 [KO:K03938 ]
623286 Ndufs6b; NADH:ubiquinone oxidoreductase subunit S6B [KO:K03939 ]
66043 Atp5f1d; ATP synthase F1 subunit delta [KO:K02134 ]
66046 Ndufb5; NADH:ubiquinone oxidoreductase subunit B5 [KO:K03961 ]
66052 Sdhc; succinate dehydrogenase complex, subunit C, integral membrane protein [KO:K00236 ]
66091 Ndufa3; NADH:ubiquinone oxidoreductase subunit A3 [KO:K03947 ]
66108 Ndufa9; NADH:ubiquinone oxidoreductase subunit A9 [KO:K03953 ]
66142 Cox7b; cytochrome c oxidase subunit 7B [KO:K02271 ]
66152 Uqcr10; ubiquinol-cytochrome c reductase, complex III subunit X [KO:K00419 ]
66218 Ndufb9; NADH:ubiquinone oxidoreductase subunit B9 [KO:K03965 ]
66377 Ndufc1; NADH:ubiquinone oxidoreductase subunit C1 [KO:K03967 ]
66413 Psmd6; proteasome (prosome, macropain) 26S subunit, non-ATPase, 6 [KO:K03037 ]
66414 Ndufa12; NADH:ubiquinone oxidoreductase subunit A12 [KO:K11352 ]
66416 Ndufa7; NADH:ubiquinone oxidoreductase subunit A7 [KO:K03951 ]
66420 Polr2e; polymerase (RNA) II (DNA directed) polypeptide E [KO:K03013 ]
66491 Polr2l; polymerase (RNA) II (DNA directed) polypeptide L [KO:K03007 ]
66495 Ndufb3; NADH:ubiquinone oxidoreductase subunit B3 [KO:K03959 ]
66576 Uqcrh; ubiquinol-cytochrome c reductase hinge protein [KO:K00416 ]
66594 Uqcr11; ubiquinol-cytochrome c reductase, complex III subunit XI [KO:K00420 ]
66694 Uqcrfs1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411 ] [EC:7.1.1.8 ]
66916 Ndufb7; NADH:ubiquinone oxidoreductase subunit B7 [KO:K03963 ]
66925 Sdhd; succinate dehydrogenase complex, subunit D, integral membrane protein [KO:K00237 ]
66945 Sdha; succinate dehydrogenase complex, subunit A, flavoprotein (Fp) [KO:K00234 ] [EC:1.3.5.1 ]
66997 Psmd12; proteasome (prosome, macropain) 26S subunit, non-ATPase, 12 [KO:K03035 ]
67003 Uqcrc2; ubiquinol cytochrome c reductase core protein 2 [KO:K00415 ]
67089 Psmc6; proteasome (prosome, macropain) 26S subunit, ATPase, 6 [KO:K03064 ]
67126 Atp5f1e; ATP synthase F1 subunit epsilon [KO:K02135 ]
67130 Ndufa6; NADH:ubiquinone oxidoreductase subunit A6 [KO:K03950 ]
67151 Psmd9; proteasome (prosome, macropain) 26S subunit, non-ATPase, 9 [KO:K06693 ]
67184 Ndufa13; NADH:ubiquinone oxidoreductase subunit A13 [KO:K11353 ]
67264 Ndufb8; NADH:ubiquinone oxidoreductase subunit B8 [KO:K03964 ]
67273 Ndufa10; NADH:ubiquinone oxidoreductase subunit A10 [KO:K03954 ]
67530 Uqcrb; ubiquinol-cytochrome c reductase binding protein [KO:K00417 ]
67680 Sdhb; succinate dehydrogenase complex, subunit B, iron sulfur (Ip) [KO:K00235 ] [EC:1.3.5.1 ]
67710 Polr2g; polymerase (RNA) II (DNA directed) polypeptide G [KO:K03015 ]
67942 Atp5mc2; ATP synthase membrane subunit c locus 2 [KO:K02128 ]
68194 Ndufb4; NADH:ubiquinone oxidoreductase subunit B4 [KO:K03960 ]
68197 Ndufc2; NADH:ubiquinone oxidoreductase subunit C2 [KO:K03968 ]
68198 Ndufb2; NADH:ubiquinone oxidoreductase subunit B2 [KO:K03958 ]
68202 Ndufa5; NADH:ubiquinone oxidoreductase subunit A5 [KO:K03949 ]
68342 Ndufb10; NADH:ubiquinone oxidoreductase subunit B10 [KO:K03966 ]
68375 Ndufa8; NADH:ubiquinone oxidoreductase subunit A8 [KO:K03952 ]
68922 Dnai1; dynein axonemal intermediate chain 1 [KO:K10409 ]
69077 Psmd11; proteasome (prosome, macropain) 26S subunit, non-ATPase, 11 [KO:K03036 ]
69241 Polr2d; polymerase (RNA) II (DNA directed) polypeptide D [KO:K03012 ]
69833 Polr2f; polymerase (RNA) II (DNA directed) polypeptide F [KO:K03014 ]
69875 Ndufa11; NADH:ubiquinone oxidoreductase subunit A11 [KO:K03956 ]
69920 Polr2i; polymerase (RNA) II (DNA directed) polypeptide I [KO:K03017 ]
69926 Dnah17; dynein, axonemal, heavy chain 17 [KO:K10408 ]
70247 Psmd1; proteasome (prosome, macropain) 26S subunit, non-ATPase, 1 [KO:K03032 ]
70316 Ndufab1; NADH:ubiquinone oxidoreductase subunit AB1 [KO:K03955 ]
71679 Atp5pd; ATP synthase peripheral stalk subunit d [KO:K02138 ]
71770 Ap2b1; adaptor-related protein complex 2, beta 1 subunit [KO:K11825 ]
72504 Taf4b; TATA-box binding protein associated factor 4b [KO:K03129 ]
73333 Slc25a31; solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 31 [KO:K05863 ]
74781 Wipi2; WD repeat domain, phosphoinositide interacting 2 [KO:K17908 ]
75483 Cox8c; cytochrome c oxidase subunit 8C [KO:K02273 ]
75563 Dnali1; dynein, axonemal, light intermediate polypeptide 1 [KO:K10410 ]
78174 Cox7b2; cytochrome c oxidase subunit 7B2 [KO:K02271 ]
78284 Creb3l4; cAMP responsive element binding protein 3-like 4 [KO:K09048 ]
78330 Ndufv3; NADH:ubiquinone oxidoreductase core subunit V3 [KO:K03944 ]
84682 Cox4i2; cytochrome c oxidase subunit 4I2 [KO:K02263 ]
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
mmu04141 Protein processing in endoplasmic reticulum
KO pathway
All links
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