| 研究課題/領域番号 |
23K19350
|
|---|
| 研究機関 | 大阪大学 |
|---|
研究代表者 |
|
|---|
| 研究期間 (年度) |
2023-08-31 – 2025-03-31
|
| キーワード | ubiquitin code / protein aggregates / aging / E3 ligase |
|---|
| 研究実績の概要 |
Protein misfolding, aggregation, and proteotoxic stresses contribute to cellular damage and disease. Ubiquitination plays a crucial role in maintaining protein homeostasis by removing toxic aggregates through the ubiquitin-proteasomal system and autophagy.
The purpose of this research is to elucidate the role of ubiquitin codes in toxic aggregate accumulation and help identify new therapeutic targets for age-related diseases to promote healthy aging.
We have found a unique ubiquitin code on toxic protein aggregates. We have established the role of a specific E3 ligase in protein aggregation under age-related stresses. We have generated and characterized unique nanobodies against the specific E3 ligase. We found that these nanobodies can modulate the formation and removal of toxic aggregates.
|
| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We have been able to establish the association between a specific E3 ligase and the accumulation of toxic protein aggregates under stresses. We have also found a unique ubiquitin code on the toxic aggregates. With the use of unique nanobodies we have been able to modulate the formation and removal of protein aggregates in cells.
Due to these significant findings we have been able to establish our hypothesis and we are progressing according to the proposed plan. We are currently establishing the mechanism underlying the E3 ligase-mediated formation of aggregates.
|
| 今後の研究の推進方策 |
So far we have been able to establish the association between a specific E3 ligase and the accumulation of toxic protein aggregates under stresses, and we have screened nanobodies to modulate toxic aggregate formation. Next we will elucidate the detailed mechanisms underlying these processes. Furthermore, we plan to use the nanobodies to identify potential targets that may be involved in aging stress-related toxic aggregate formation. With this information we will screen these potential targets in search of proteins that may mitigate the formation of toxic aggregates under stresses.
|
| 次年度使用額が生じた理由 |
Consumables and other supplies were able to be purchased with the University operating subsidy, and the planned amount was not used. This fiscal year, there is a plan to use the funds, and we plan to use them systematically.
|
