Nature Communications (Jul 2022)
Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance
- Lidia Wrobel,
- Sandra M. Hill,
- Alvin Djajadikerta,
- Marian Fernandez-Estevez,
- Cansu Karabiyik,
- Avraham Ashkenazi,
- Victoria J. Barratt,
- Eleanna Stamatakou,
- Anders Gunnarsson,
- Timothy Rasmusson,
- Eric W. Miele,
- Nigel Beaton,
- Roland Bruderer,
- Yuehan Feng,
- Lukas Reiter,
- M. Paola Castaldi,
- Rebecca Jarvis,
- Keith Tan,
- Roland W. Bürli,
- David C. Rubinsztein
Affiliations
- Lidia Wrobel
- Department of Medical Genetics, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus
- Sandra M. Hill
- Department of Medical Genetics, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus
- Alvin Djajadikerta
- Department of Medical Genetics, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus
- Marian Fernandez-Estevez
- Department of Medical Genetics, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus
- Cansu Karabiyik
- Department of Medical Genetics, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus
- Avraham Ashkenazi
- Department of Medical Genetics, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus
- Victoria J. Barratt
- Department of Medical Genetics, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus
- Eleanna Stamatakou
- Department of Medical Genetics, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus
- Anders Gunnarsson
- Biophysics SE, Discovery Sciences, R&D, AstraZeneca
- Timothy Rasmusson
- Discovery Biology, Discovery Sciences, R&D, AstraZeneca
- Eric W. Miele
- Discovery Biology, Discovery Sciences, R&D, AstraZeneca
- Nigel Beaton
- Biognosys AG
- Roland Bruderer
- Biognosys AG
- Yuehan Feng
- Biognosys AG
- Lukas Reiter
- Biognosys AG
- M. Paola Castaldi
- Discovery Biology, Discovery Sciences, R&D, AstraZeneca
- Rebecca Jarvis
- Discovery UK, Neuroscience, BioPharmaceuticals R&D, AstraZeneca
- Keith Tan
- Discovery UK, Neuroscience, BioPharmaceuticals R&D, AstraZeneca
- Roland W. Bürli
- Discovery UK, Neuroscience, BioPharmaceuticals R&D, AstraZeneca
- David C. Rubinsztein
- Department of Medical Genetics, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus
- DOI
- https://doi.org/10.1038/s41467-022-31905-0
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 19
Abstract
Several neurodegenerative diseases are characterized by the aggregation of cytoplasmic proteins. Here, the authors demonstrate that the small molecule SMER28 activates VCP, which enhances both autophagic and proteasomal clearance of aggregate-prone proteins.
