| First Author | Zamponi E | Year | 2018 |
| Journal | Aging Cell | Volume | 17 |
| Issue | 5 | Pages | e12812 |
| PubMed ID | 30028071 | Mgi Jnum | J:265457 |
| Mgi Id | MGI:6200448 | Doi | 10.1111/acel.12812 |
| Citation | Zamponi E, et al. (2018) Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells. Aging Cell 17(5):e12812 |
| abstractText | Mounting evidence implicates chronic oxidative stress as a critical driver of the aging process. Down syndrome (DS) is characterized by a complex phenotype, including early senescence. DS cells display increased levels of reactive oxygen species (ROS) and mitochondrial structural and metabolic dysfunction, which are counterbalanced by sustained Nrf2-mediated transcription of cellular antioxidant response elements (ARE). Here, we show that caspase 3/PKCdeltadependent activation of the Nrf2 pathway in DS and Dp16 (a mouse model of DS) cells is necessary to protect against chronic oxidative damage and to preserve cellular functionality. Mitochondria-targeted catalase (mCAT) significantly reduced oxidative stress, restored mitochondrial structure and function, normalized replicative and wound healing capacity, and rendered the Nrf2-mediated antioxidant response dispensable. These results highlight the critical role of Nrf2/ARE in the maintenance of DS cell homeostasis and validate mitochondrial-specific interventions as a key aspect of antioxidant and antiaging therapies. |
