Lookup NU author(s): Professor Tiago Outeiro
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© 2017 Elsevier Inc. Proper and efficient differentiation of dopaminergic (DA) neurons is essential for the cell-based dopamine replacement strategies that have become an attractive therapeutical option in Parkinson's disease, a disorder typically known for the degeneration of the nigral DA neurons. Here, we established that the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 2 (SIRT2) interacts with protein kinase B, and, via the glycogen synthase kinase 3β/β-catenin pathway, modulates the differentiation of DA neurons. Deletion of SIRT2 resulted in a decreased number of DA neurons in the substantia nigra and lower striatal fiber density in SIRT2 knock-out mice. Similarly, we found a decreased ratio of DA neurons in primary midbrain cultures treated with the SIRT2 inhibitor AK-7. Using protein kinase B and glycogen synthase kinase 3β inhibitors, we found that those molecules act downstream of SIRT2. Thus, SIRT2 acts as a novel regulator of the differentiation process of DA neurons, further supporting its potential as a therapeutic target in Parkinson's disease.
Author(s): Szego EM, Gerhardt E, Outeiro TF
Publication type: Article
Publication status: Published
Journal: Neurobiology of Aging
Print publication date: 01/08/2017
Online publication date: 10/04/2017
Acceptance date: 01/04/2017
ISSN (print): 0197-4580
ISSN (electronic): 1558-1497
Publisher: Elsevier Inc.
PubMed id: 28478325
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