English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  The mechanism of sirtuin 2–mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease.

de Oliveira, R. M., Miranda, H. V., Francelle, L., Pinho, R., Szegö, E. M., Martinho, R., et al. (2017). The mechanism of sirtuin 2–mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease. PLoS Biology, 15(3): e2000374. doi:10.1371/journal.pbio.2000374.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-E85B-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-E85F-9
Genre: Journal Article

Files

show Files
hide Files
:
2418345.pdf (Publisher version), 3MB
Name:
2418345.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
:
2418345_Suppl.htm (Supplementary material), 273KB
Name:
2418345_Suppl.htm
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/xhtml+xml / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
de Oliveira, R. M., Author
Miranda, H. V., Author
Francelle, L., Author
Pinho, R., Author
Szegö, E. M., Author
Martinho, R., Author
Munari, F.1, Author              
Lázaro, D. F., Author
Moniot, S., Author
Guerreiro, P., Author
Fonseca, L.1, Author              
Marijanovic, Z., Author
Antas, P., Author
Gerhardt, E., Author
Enguita, F. J., Author
Fauvet, B., Author
Penque, D., Author
Pais, T. F., Author
Tong, Q., Author
Becker, S.2, Author              
Kügler, S., AuthorLashuel, H. A., AuthorSteegborn, C., AuthorZweckstetter, M.1, Author              Outeiro, T. F., Author more..
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              
2Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society, ou_578567              

Content

show
hide
Free keywords: -
 Abstract: 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

Details

show
hide
Language(s): eng - English
 Dates: 2017-03-03
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1371/journal.pbio.2000374
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: PLoS Biology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: 27 Volume / Issue: 15 (3) Sequence Number: e2000374 Start / End Page: - Identifier: -