+検索条件
-Structure paper
タイトル | Huntington's disease cerebrospinal fluid seeds aggregation of mutant huntingtin. |
---|---|
ジャーナル・号・ページ | Mol Psychiatry, Vol. 20, Issue 11, Page 1286-1293, Year 2015 |
掲載日 | 2015年6月23日 |
著者 | Z Tan / W Dai / T G M van Erp / J Overman / A Demuro / M A Digman / A Hatami / R Albay / E M Sontag / K T Potkin / S Ling / F Macciardi / W E Bunney / J D Long / J S Paulsen / J M Ringman / I Parker / C Glabe / L M Thompson / W Chiu / S G Potkin / |
PubMed 要旨 | Huntington's disease (HD), a progressive neurodegenerative disease, is caused by an expanded CAG triplet repeat producing a mutant huntingtin protein (mHTT) with a polyglutamine-repeat expansion. ...Huntington's disease (HD), a progressive neurodegenerative disease, is caused by an expanded CAG triplet repeat producing a mutant huntingtin protein (mHTT) with a polyglutamine-repeat expansion. Onset of symptoms in mutant huntingtin gene-carrying individuals remains unpredictable. We report that synthetic polyglutamine oligomers and cerebrospinal fluid (CSF) from BACHD transgenic rats and from human HD subjects can seed mutant huntingtin aggregation in a cell model and its cell lysate. Our studies demonstrate that seeding requires the mutant huntingtin template and may reflect an underlying prion-like protein propagation mechanism. Light and cryo-electron microscopy show that synthetic seeds nucleate and enhance mutant huntingtin aggregation. This seeding assay distinguishes HD subjects from healthy and non-HD dementia controls without overlap (blinded samples). Ultimately, this seeding property in HD patient CSF may form the basis of a molecular biomarker assay to monitor HD and evaluate therapies that target mHTT. |
リンク | Mol Psychiatry / PubMed:26100538 / PubMed Central |
手法 | EM (トモグラフィー) |
構造データ | EMDB-2991: |
由来 |
|