Reference - Detail
| RRC ID | 2391 |
|---|---|
| Author | Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H, Kurosawa M, Nekooki M, Nukina N. |
| Title | Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. |
| Journal | 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. |
| Volume | 10(2) |
| Pages | 148-54 |
| Published | 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 |
| Times Cited | 502 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY MEDICINE, RESEARCH & EXPERIMENTAL CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 40 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC00050 |