光でタンパク質の「凝縮」と「溶解」を自在に操る新技術を開発~ALSやアルツハイマー病などの治療法開発を加速する技術基盤~

ad

2026-04-20 徳島大学

徳島大学の研究チームは、光によってタンパク質の凝縮(相分離)と溶解を自在に制御できる新技術「OptoChaperone」を開発した。細胞内ではタンパク質が液滴状に集まる相分離が機能制御に重要だが、その解消ができないと異常凝集を引き起こし、筋萎縮性側索硬化症やアルツハイマー病などの神経変性疾患に関与する。本技術は光照射により液滴の形成と解消を可逆的に操作でき、従来困難だった「凝縮後の解消」の制御を実現した。これにより、相分離と病的凝集の因果関係を精密に解析可能となり、発症機構の理解が進むと期待される。将来的には、神経変性疾患の新たな治療法開発を支える基盤技術となる可能性がある。

光でタンパク質の「凝縮」と「溶解」を自在に操る新技術を開発~ALSやアルツハイマー病などの治療法開発を加速する技術基盤~
図1. OptoChaperone の概念図

<関連情報>

オプトシャペロン – 細胞内と試験管内のタンパク質凝縮体を制御するバイオハイブリッドツール OptoChaperone─A Biohybrid Tool for Regulating Protein Condensates in Cells and In Vitro

Do Thanh Tuan,Motonori Matsusaki,Honoka Ota,Soichiro Kawagoe,Hettimudalige Dilini Nisansala,Munehiro Kumashiro,Noriyoshi Isozumi,Hiroyuki Kumeta,Yohei Kono,Takeshi Shimi,Koichiro Ishimori,Eiichiro Mori,Satoshi Arai,and Tomohide Saio
Journal of the American Chemical Society  Published: April 19, 2026
DOI:https://doi.org/10.1021/jacs.6c04074

Abstract

Protein condensates formed via liquid–liquid phase separation (LLPS) are increasingly recognized as key players in diverse cellular processes, including those associated with disease. Despite extensive efforts to characterize their formation and function, tools that enable precise, reversible, and spatiotemporal control of LLPS remain limited. Here, we report OptoChaperone, a light-activatable molecular system designed to manipulate protein condensates both in vitro and in living cells. This biohybrid system leverages photoresponsive switching to control chaperone activity: blue light triggers the suppressive function, leading to the dissolution of protein condensates, whereas UV light deactivates the system, allowing condensate formation. We demonstrate the efficacy of OptoChaperone in regulating several disease-related protein condensates, such as fused in sarcoma, TAR DNA-binding protein 43, and heat shock factor 1. Importantly, the system exhibits reversible and robust control over droplet dynamics without requiring chemical additives or genetic modifications of the client proteins. Given the reversibility and efficiency of OptoChaperone in the manipulation of protein condensates, this tool offers a powerful platform for dissecting the roles of protein condensation in cellular physiology and pathology. This strategy also holds potential for broader applications in synthetic biology, biomolecular engineering, and therapeutic modulation of aberrant phase separation.

細胞遺伝子工学
ad
ad
Follow
ad
タイトルとURLをコピーしました