| Entry |
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| Name |
Huntington disease |
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| 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 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.
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| Category |
Neurodegenerative disease
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| Brite |
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
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| Pathway |
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| Network |
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| Element |
| 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 |
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| Gene |
HTT; huntingtin (CAG repeat expansion) [HSA: 3064] [KO: K04533]
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| Drug |
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| Comment |
Disease class: polyglutamine disease
Affected region: caudate nucleus, globus pallidus, thalamus, hippocampus
Microscopic lesion: neuronal intranuclear inclusions
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| Other DBs |
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| Reference |
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| Authors |
Imarisio S, Carmichael J, Korolchuk V, Chen CW, Saiki S, Rose C, Krishna G, Davies JE, Ttofi E, Underwood BR, Rubinsztein DC |
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| Title |
Huntington's disease: from pathology and genetics to potential therapies. |
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| Journal |
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| Reference |
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| Authors |
Spires TL, Hannan AJ |
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| Title |
Molecular mechanisms mediating pathological plasticity in Huntington's disease and Alzheimer's disease. |
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| Journal |
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| Reference |
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| Authors |
Gusella JF, Macdonald ME |
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| Title |
Huntington's disease: seeing the pathogenic process through a genetic lens. |
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| Journal |
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| Reference |
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| Authors |
Gardian G, Vecsei L. |
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| Title |
Huntington's disease: pathomechanism and therapeutic perspectives. |
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| Journal |
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