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The sirtuin-2 inhibitor AK7 is neuroprotective in models of Parkinson's disease but not amyotrophic lateral sclerosis and cerebral ischemia.

Title data

Chen, Xiqun ; Wales, Pauline ; Quinti, Luisa ; Zuo, Fuxing ; Moniot, Sébastien ; Herisson, Fanny ; Rauf, Nazifa Abdul ; Wang, Hua ; Silverman, Richard B. ; Ayata, Cenk ; Maxwell, Michelle M. ; Steegborn, Clemens ; Schwarzschild, Michael A. ; Outeiro, Tiago F. ; Kazantsev, Aleksey G.:
The sirtuin-2 inhibitor AK7 is neuroprotective in models of Parkinson's disease but not amyotrophic lateral sclerosis and cerebral ischemia.
In: PLoS One. Vol. 10 (2015) Issue 1 . - e0116919.
ISSN 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0116919

Abstract in another language

Sirtuin deacetylases regulate diverse cellular pathways and influence disease processes. Our previous studies identified the brain-enriched sirtuin-2 (SIRT2) deacetylase as a potential drug target to counteract neurodegeneration. In the present study, we characterize SIRT2 inhibition activity of the brain-permeable compound AK7 and examine the efficacy of this small molecule in models of Parkinson's disease, amyotrophic lateral sclerosis and cerebral ischemia. Our results demonstrate that AK7 is neuroprotective in models of Parkinson's disease; it ameliorates alpha-synuclein toxicity in vitro and prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine depletion and dopaminergic neuron loss in vivo. The compound does not show beneficial effects in mouse models of amyotrophic lateral sclerosis and cerebral ischemia. These findings underscore the specificity of protective effects observed here in models of Parkinson's disease, and previously in Huntington's disease, and support the development of SIRT2 inhibitors as potential therapeutics for the two neurodegenerative diseases.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 23248282
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: Yes
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 20 Apr 2015 14:41
Last Modified: 20 Apr 2015 14:41
URI: https://eref.uni-bayreuth.de/id/eprint/10435