| H00059 | |
| H番号 | H00059 |
| 名称 | ハンチントン病 |
| 概要 | 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. |
| カテゴリ | 神経変性疾患 疾患パスウェイ hsa05016 ハンチントン病 |
| ネットワーク | nt06410(H00059) Calcium signaling nt06413(H00059) Autophagy nt06414(H00059) Apoptosis nt06416(H00059) TNF signaling nt06418(H00059) Oxidative phosphorylation nt06419(H00059) Microtubule-based transport nt06420(H00059) Ubiquitin-proteasome system nt06440(H00059) Transcription nt06461 Huntington disease |
| 病因遺伝子 | (HD) HTT [HSA:3064] [KO:K04533] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | テトラベナジン [DR:D08575] |
| コメント | Disease class: polyglutamine disease Affected region: caudate nucleus, globus pallidus, thalamus, hippocampus Microscopic lesion: neuronal intranuclear inclusions |
| リンク | ICD-11: 8A01.10 ICD-10: G10 MeSH: D006816 OMIM: 143100 |
| 文献 | PMID:18466116 著者 Imarisio S, Carmichael J, Korolchuk V, Chen CW, Saiki S, Rose C, Krishna G, Davies JE, Ttofi E, Underwood BR, Rubinsztein DC タイトル Huntington's disease: from pathology and genetics to potential therapies. 雑誌 Biochem J 412:191-209 (2008) DOI:10.1042/BJ20071619 PMID:17217424 著者 Spires TL, Hannan AJ タイトル Molecular mechanisms mediating pathological plasticity in Huntington's disease and Alzheimer's disease. 雑誌 J Neurochem 100:874-82 (2007) DOI:10.1111/j.1471-4159.2006.04275.x PMID:16829072 著者 Gusella JF, Macdonald ME タイトル Huntington's disease: seeing the pathogenic process through a genetic lens. 雑誌 Trends Biochem Sci 31:533-40 (2006) DOI:10.1016/j.tibs.2006.06.009 PMID:15480847 著者 Gardian G, Vecsei L. タイトル Huntington's disease: pathomechanism and therapeutic perspectives. 雑誌 J Neural Transm 111:1485-94 (2004) DOI:10.1007/s00702-004-0201-4 PMID:8458085 (HD) タイトル A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. 雑誌 Cell 72:971-83 (1993) DOI:10.1016/0092-8674(93)90585-e |