KEGG   DISEASE: Huntington disease
H00059                      Disease                                

Huntington disease
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 Htt 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.
Neurodegenerative disease
Human diseases [BR:br08402]
 Nervous system diseases
  Neurodegenerative diseases
   H00059  Huntington disease
Human diseases in ICD-11 classification [BR:br08403]
 08 Diseases of the nervous system
  Movement disorders
   8A01  Choreiform disorders
    H00059  Huntington disease
hsa05016  Huntington disease
nt06410  Calcium signaling
nt06413  Autophagy
nt06414  Apoptosis
nt06416  TNF signaling
nt06418  Oxidative phosphorylation
nt06419  Microtubule-based transport
nt06420  Ubiquitin-proteasome system
nt06440  Transcription
nt06461  Huntington disease
N00977  Mutation-caused aberrant Htt to retrograde axonal transport
N00979  Mutation-caused aberrant Htt to anterograde axonal transport
N00980  Mutation-caused aberrant Htt to REST-mediated transcriptional repression
N00981  Mutation-caused aberrant Htt to CREB-mediated transcription
N00982  Mutation-caused aberrant Htt to p53-mediated transcription
N00983  Mutation-caused aberrant Htt to extrinsic apoptotic pathway
N00985  Mutation-caused aberrant Htt to mGluR5-Ca2+ -apoptotic pathway
N00986  Mutation-caused aberrant Htt to VGCC-Ca2+ -apoptotic pathway
N00987  Mutation-caused aberrant Htt to transport of calcium
N00989  Mutation-caused aberrant Htt to electron transfer in Complex II
N00991  Mutation-caused aberrant Htt to electron transfer in Complex III
N00992  Mutation-caused aberrant Htt to TNF-JNK signaling pathway
N00993  Mutation-caused aberrant Htt to autophagy-vesicle nucleation
N01061  Mutation-caused aberrant Htt to 26S proteasome-mediated protein degradation
HTT; huntingtin (CAG repeat expansion) [HSA:3064] [KO:K04533]
Tetrabenazine [DR:D08575]
Deutetrabenazine [DR:D10701]
Disease class: polyglutamine disease
Affected region: caudate nucleus, globus pallidus, thalamus, hippocampus
Microscopic lesion: neuronal intranuclear inclusions
Other DBs
ICD-11: 8A01.10
ICD-10: G10
MeSH: D006816
OMIM: 143100
Imarisio S, Carmichael J, Korolchuk V, Chen CW, Saiki S, Rose C, Krishna G, Davies JE, Ttofi E, Underwood BR, Rubinsztein DC
Huntington's disease: from pathology and genetics to potential therapies.
Biochem J 412:191-209 (2008)
Spires TL, Hannan AJ
Molecular mechanisms mediating pathological plasticity in Huntington's disease and Alzheimer's disease.
J Neurochem 100:874-82 (2007)
Gusella JF, Macdonald ME
Huntington's disease: seeing the pathogenic process through a genetic lens.
Trends Biochem Sci 31:533-40 (2006)
Gardian G, Vecsei L.
Huntington's disease: pathomechanism and therapeutic perspectives.
J Neural Transm 111:1485-94 (2004)

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