| H00059 | |
| H number | H00059 |
| Name | Huntington disease |
| 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 stretch translocate to the nucleus where they impair transcription and induce neuronal death. |
| Category | Neurodegenerative disease DIS_PATHWAY hsa05016 Huntington disease |
| Network | nt06461 Huntington disease |
| Gene | (HD) HTT [HSA:3064] [KO:K04533] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | Tetrabenazine [DR:D08575] Deutetrabenazine [DR:D10701] |
| Comment | 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 |
| Reference | PMID:18466116 AUTHORS Imarisio S, Carmichael J, Korolchuk V, Chen CW, Saiki S, Rose C, Krishna G, Davies JE, Ttofi E, Underwood BR, Rubinsztein DC TITLE Huntington's disease: from pathology and genetics to potential therapies. JOURNAL Biochem J 412:191-209 (2008) DOI:10.1042/BJ20071619 PMID:17217424 AUTHORS Spires TL, Hannan AJ TITLE Molecular mechanisms mediating pathological plasticity in Huntington's disease and Alzheimer's disease. JOURNAL J Neurochem 100:874-82 (2007) DOI:10.1111/j.1471-4159.2006.04275.x PMID:16829072 AUTHORS Gusella JF, Macdonald ME TITLE Huntington's disease: seeing the pathogenic process through a genetic lens. JOURNAL Trends Biochem Sci 31:533-40 (2006) DOI:10.1016/j.tibs.2006.06.009 PMID:15480847 AUTHORS Gardian G, Vecsei L. TITLE Huntington's disease: pathomechanism and therapeutic perspectives. JOURNAL J Neural Transm 111:1485-94 (2004) DOI:10.1007/s00702-004-0201-4 PMID:8458085 (HD) TITLE A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. JOURNAL Cell 72:971-83 (1993) DOI:10.1016/0092-8674(93)90585-e |