| RRC ID |
2391
|
| 著者 |
Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H, Kurosawa M, Nekooki M, Nukina N.
|
| タイトル |
Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease.
|
| ジャーナル |
Nat Med
|
| Abstract |
Inhibition of polyglutamine-induced protein aggregation could provide treatment options for polyglutamine diseases such as Huntington disease. Here we showed through in vitro screening studies that various disaccharides can inhibit polyglutamine-mediated protein aggregation. We also found that various disaccharides reduced polyglutamine aggregates and increased survival in a cellular model of Huntington disease. Oral administration of trehalose, the most effective of these disaccharides, decreased polyglutamine aggregates in cerebrum and liver, improved motor dysfunction and extended lifespan in a transgenic mouse model of Huntington disease. We suggest that these beneficial effects are the result of trehalose binding to expanded polyglutamines and stabilizing the partially unfolded polyglutamine-containing protein. Lack of toxicity and high solubility, coupled with efficacy upon oral administration, make trehalose promising as a therapeutic drug or lead compound for the treatment of polyglutamine diseases. The saccharide-polyglutamine interaction identified here thus provides a new therapeutic strategy for polyglutamine diseases.
|
| 巻・号 |
10(2)
|
| ページ |
148-54
|
| 公開日 |
2004-2-1
|
| DOI |
10.1038/nm985
|
| PII |
nm985
|
| PMID |
14730359
|
| MeSH |
Animals
Brain / cytology
Brain / metabolism
Brain / pathology
Cell Death / physiology
Cell Line
Disease Models, Animal
Glucose / administration & dosage
Glucose / metabolism
Humans
Huntingtin Protein
Huntington Disease / drug therapy*
Huntington Disease / metabolism
Huntington Disease / pathology*
Liver / cytology
Liver / metabolism
Liver / pathology
Mice
Mice, Transgenic
Motor Activity / physiology
Myoglobin / genetics
Myoglobin / metabolism
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Neurons / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Peptides / metabolism*
Trehalose / therapeutic use*
|
| IF |
36.13
|
| 引用数 |
502
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
MEDICINE, RESEARCH & EXPERIMENTAL
CELL BIOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00050 |
