論文 - 詳細
| RRC ID | 54285 |
|---|---|
| 著者 | van Ham TJ, Holmberg MA, van der Goot AT, Teuling E, Garcia-Arencibia M, Kim HE, Du D, Thijssen KL, Wiersma M, Burggraaff R, van Bergeijk P, van Rheenen J, Jerre van Veluw G, Hofstra RM, Rubinsztein DC, Nollen EA. |
| タイトル | Identification of MOAG-4/SERF as a regulator of age-related proteotoxicity. |
| ジャーナル | Cell |
| Abstract |
Fibrillar protein aggregates are the major pathological hallmark of several incurable, age-related, neurodegenerative disorders. These aggregates typically contain aggregation-prone pathogenic proteins, such as amyloid-beta in Alzheimer's disease and alpha-synuclein in Parkinson's disease. It is, however, poorly understood how these aggregates are formed during cellular aging. Here we identify an evolutionarily highly conserved modifier of aggregation, MOAG-4, as a positive regulator of aggregate formation in C. elegans models for polyglutamine diseases. Inactivation of MOAG-4 suppresses the formation of compact polyglutamine aggregation intermediates that are required for aggregate formation. The role of MOAG-4 in driving aggregation extends to amyloid-beta and alpha-synuclein and is evolutionarily conserved in its human orthologs SERF1A and SERF2. MOAG-4/SERF appears to act independently from HSF-1-induced molecular chaperones, proteasomal degradation, and autophagy. Our results suggest that MOAG-4/SERF regulates age-related proteotoxicity through a previously unexplored pathway, which will open up new avenues for research on age-related, neurodegenerative diseases. |
| 巻・号 | 142(4) |
| ページ | 601-12 |
| 公開日 | 2010-8-20 |
| DOI | 10.1016/j.cell.2010.07.020 |
| PII | S0092-8674(10)00789-0 |
| PMID | 20723760 |
| MeSH | Amyloid beta-Peptides / metabolism Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / metabolism* Cell Line Cell Line, Tumor Cellular Senescence* Humans Intracellular Signaling Peptides and Proteins Mice Nerve Tissue Proteins / chemistry Nerve Tissue Proteins / metabolism* Neurodegenerative Diseases / metabolism* Peptides / metabolism Proteins / chemistry Proteins / metabolism* alpha-Synuclein / metabolism |
| IF | 38.637 |
| 引用数 | 58 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm4909 |