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International Affairs Students Current Students Alumni Faculty/Staff Careers--> TOHOKU UNIVERSITYCREATING GLOBAL EXCELLENCE Search 日本語 Contact Tohoku University --> About Facts & Figures Facilities Organization Chart History President's Message Top Global University Project Designated National University Global Network Promotional Videos Academics Undergraduate Graduate Courses in English Exchange Programs Summer Programs Double Degree Programs Academic Calendar Syllabus Admissions Undergraduate Admissions Graduate Admissions Fees and Expenses Financial Aid Research Feature Highlights Research Releases University Research News Research Institutes Visitor Research Center Research Profiles Academic Research Staff Campus Life International Support Office IT Services Facilities Dining & Shops Campus Bus Clubs & Circles News University News Research--> Arts & Culture Health & Sports Campus & Community Press Release--> International Visit Alumni Careers Events Exhibits Music Special Event Lecture Alumni--> Map & Directions Campus Maps & Bus--> Facilities Map--> TOHOKUUNIVERSITY About Academics Admissions Research Campus Life News Events International Affairs Students Current Students Alumni Faculty/Staff Promotional Videos Subscribe to our Newsletter Map & Directions Contact Jobs & Vacancies Emergency Information Site Map 日本語 Close Home Research News The Molecule that Can AUTAC Bad Proteins Research News The Molecule that Can AUTAC Bad Proteins 2019-11-27 Tohoku University researchers have developed a strategy that could help cells get rid of disease-related debris. Further research could lead to treatments for neurodegenerative and metabolic diseases, Down syndrome, and maybe even aging-related diseases. The findings were published in the journal Molecular Cell. Cells have a natural ability to routinely rid themselves of unnecessary or dysfunctional proteins and organelles. During this process of 'autophagy', debris are tagged with a compound called ubiquitin and then degraded within tiny cellular vacuoles. Autophagy is impaired in some cancers, and neurodegenerative and metabolic diseases, so scientists have been working to develop drugs that can regulate this process. However, little is known about the details of autophagy, such as how the cell knows which components to tag with ubiquitin. In previous research, Hirokazu Arimoto, a chemical biologist at Tohoku University, and colleagues found that autophagy is initiated against invading streptococci bacteria when they are tagged with the nucleic acid guanine. The researchers wondered if guanine tagging could also initiate autophagy against other cellular components. Their investigations led to the development of a molecule they called AUTAC, which stands for autophagy-targeting chimera. AUTAC is formed of guanine attached to a 'warhead', which can be changed to target specific intracellular components. Different AUTACs successfully targeted and tagged specific intracellular proteins for autophagy, the researchers report. AUTAC is formed of guanine attached to a protein-specific warhead ⒸTohoku University For example, they designed an AUTAC targeting a protein on the mitochondrial membrane. Mitochondrial dysfunction causes some symptoms frequently seen in Down syndrome, including heart disease, hearing loss and dementia. It also causes several diseases associated with aging. The AUTAC successfully targeted fragmented mitochondria in cells taken from someone with Down syndrome. Not only did this accelerate their removal, it also fast-tracked the formation of new, normally functioning mitochondria. AUTAC successfully led to the removal of bad mitochondria and fast-tracked the formation of new, healthy ones. ⒸTohoku University "AUTAC degrades its target, making it a game-changing innovation for the drug industry," says Arimoto. "Current small molecule drugs bind to molecules, like proteins, and interfere with their functions, but do not degrade them. The degradation of biomolecules gets rid of all the functions and is a more powerful method." Arimoto and his team are now working on developing second-generation AUTAC molecules that will be at least 100 times more effective, he says. Publication Details: Title: AUTACs: Cargo-Specific Degraders Using Selective AutophagyAuthors: Daiki Takahashi, Jun Moriyama, Tomoe Nakamura, Erika Miki, Eriko Takahashi, Ayami Sato, Takaaki Akaike, Kaori Itto-Nakama, and Hirokazu ArimotoJournal: Molecular CellDOI: 10.1016/j.molcel.2019.09.009 Press release in Japanese Contact: Hirokazu ArimotoGraduate School of Life Sciences, Tohoku UniversityEmail: arimototohoku.ac.jp Website: https://www.agri.tohoku.ac.jp/bunseki/index-j.html Archives 2014&＃24180; 2015&＃24180; 2016&＃24180; 2017&＃24180; 2018&＃24180; 2019&＃24180; 2020&＃24180; 2021&＃24180; 2022&＃24180; 2023&＃24180; Page Top About Tohoku University Academics Admissions Research Campus Life News Events International Affairs Students Alumni Promotional Videos Subscribe to our Newsletter Map & Directions Contact Tohoku University Jobs & Vacancies Emergency Information Site Map Media Enquiries Parent & Family Support Public Facilities Contact Tohoku University