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Sirtuin 2 enhances dopaminergic differentiation via the AKT/GSK-3β/β-catenin pathway

Lookup NU author(s): Professor Tiago Outeiro

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Abstract

© 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.


Publication metadata

Author(s): Szego EM, Gerhardt E, Outeiro TF

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2017

Volume: 56

Pages: 7-16

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.

URL: https://doi.org/10.1016/j.neurobiolaging.2017.04.001

DOI: 10.1016/j.neurobiolaging.2017.04.001

PubMed id: 28478325


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