Publisher Correction: Deubiquitinase Usp12 functions noncatalytically to induce autophagy and confer neuroprotection in models of Huntington’s disease
| Autor: | Aron, Rebecca, Pellegrini, Pasquale, Green, Edward W, Maddison, Daniel C, Opoku-Nsiah, Kwadwo, Oliveira, Ana Osório, Wong, Jinny S, Daub, Aaron C, Giorgini, Flaviano, Muchowski, Paul, Finkbeiner, Steven |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Science
General Physics and Astronomy General Biochemistry Genetics and Molecular Biology Autophagy Animals Humans lcsh:Science Cells Cultured Neurons Huntingtin Protein Multidisciplinary Huntington's disease General Chemistry Publisher Correction Neuroprotection Rats Drosophila melanogaster HEK293 Cells Huntington Disease Gene Expression Regulation Enzyme mechanisms Mutation RNA Interference lcsh:Q Ubiquitin Thiolesterase |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-1 (2020) Nature communications, vol 11, iss 1 Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-16216-6 |
| Popis: | Huntington's disease is a progressive neurodegenerative disorder caused by polyglutamine-expanded mutant huntingtin (mHTT). Here, we show that the deubiquitinase Usp12 rescues mHTT-mediated neurodegeneration in Huntington's disease rodent and patient-derived human neurons, and in Drosophila. The neuroprotective role of Usp12 may be specific amongst related deubiquitinases, as the closely related homolog Usp46 does not suppress mHTT-mediated toxicity. Mechanistically, we identify Usp12 as a potent inducer of neuronal autophagy. Usp12 overexpression accelerates autophagic flux and induces an approximately sixfold increase in autophagic structures as determined by ultrastructural analyses, while suppression of endogenous Usp12 slows autophagy. Surprisingly, the catalytic activity of Usp12 is not required to protect against neurodegeneration or induce autophagy. These findings identify the deubiquitinase Usp12 as a regulator of neuronal proteostasis and mHTT-mediated neurodegeneration. |
| Databáze: | OpenAIRE |
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