Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells. Academic Article uri icon

Overview

abstract

  • 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/PKCĪ“dependent 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.

publication date

  • July 20, 2018

Research

keywords

  • Down Syndrome
  • NF-E2-Related Factor 2
  • Oxidative Stress

Identity

PubMed Central ID

  • PMC6156351

Scopus Document Identifier

  • 85050345063

Digital Object Identifier (DOI)

  • 10.3233/JAD-2012-120073

PubMed ID

  • 30028071

Additional Document Info

volume

  • 17

issue

  • 5