| First Author | Szegő ÉM | Year | 2017 |
| Journal | Neurobiol Aging | Volume | 56 |
| Pages | 7-16 | PubMed ID | 28478325 |
| Mgi Jnum | J:249201 | Mgi Id | MGI:6093259 |
| Doi | 10.1016/j.neurobiolaging.2017.04.001 | Citation | Szego EM, et al. (2017) Sirtuin 2 enhances dopaminergic differentiation via the AKT/GSK-3beta/beta-catenin pathway. Neurobiol Aging 56:7-16 |
| abstractText | 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 3beta/beta-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 3beta 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. |
