at Google ScholarTitle data
de Oliveira, Rita Machado ; Vicente Miranda, Hugo ; Francelle, Laetitia ; Pinho, Raquel ; Szegö, Éva M. ; Martinho, Renato ; Munari, Francesca ; Lázaro, Diana F. ; Moniot, Sébastien ; Guerreiro, Patrícia ; Fonseca, Luis ; Marijanovic, Zrinka ; Antas, Pedro ; Gerhardt, Ellen ; Enguita, Francisco Javier ; Fauvet, Bruno ; Penque, Deborah ; Pais, Teresa Faria ; Tong, Qiang ; Becker, Stefan ; Kügler, Sebastian ; Lashuel, Hilal Ahmed ; Steegborn, Clemens ; Zweckstetter, Markus ; Outeiro, Tiago F.:
The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease.
In: PLoS Biology.
Vol. 15
(2017)
Issue 3
.
- No. e2000374.
ISSN 1545-7885
DOI: https://doi.org/10.1371/journal.pbio.2000374
Abstract in another language
Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with age-associated neurodegenerative disorders such as Alzheimer and Parkinson disease (PD). However, the precise molecular mechanisms involved remain unclear. Here, we provide mechanistic insight into the interplay between sirtuin 2 and α-synuclein, the major component of the pathognomonic protein inclusions in PD and other synucleinopathies. We found that α-synuclein is acetylated on lysines 6 and 10 and that these residues are deacetylated by sirtuin 2. Genetic manipulation of sirtuin 2 levels in vitro and in vivo modulates the levels of α-synuclein acetylation, its aggregation, and autophagy. Strikingly, mutants blocking acetylation exacerbate α-synuclein toxicity in vivo, in the substantia nigra of rats. Our study identifies α-synuclein acetylation as a key regulatory mechanism governing α-synuclein aggregation and toxicity, demonstrating the potential therapeutic value of sirtuin 2 inhibition in synucleinopathies.
Further data
| Item Type: | Article in a journal |
|---|---|
| Refereed: | Yes |
| Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Clemens Steegborn Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry |
| Result of work at the UBT: | No |
| DDC Subjects: | 500 Science > 540 Chemistry 500 Science > 570 Life sciences, biology |
| Date Deposited: | 06 Apr 2017 08:47 |
| Last Modified: | 31 Aug 2022 13:56 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/36765 |