English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Ataxia‐telangiectasia (A‐T) is a genetic disorder caused by a mutation of the  Atm  gene, which controls DNA repair, cell cycling, and redox homeostasis. Even though oxidative stress has been implicated in the neurological anomalies in A‐T, the effects of ATM loss on neural stem cell (NSC) survival has remained elusive. In this study, we investigated the effects of oxidative stress on NSC proliferation in an animal model for A‐T neurodegeneration. We found that cultured subventricular zone neurosphere cells from  Atm  −/−  mice show impaired proliferation, as well as intrinsic elevation of reactive oxygen species (ROS) levels, compared with those from  Atm  +/+  mice. We also show that increasing the levels of ROS by H 2 O 2  treatment significantly reduces  Atm  +/+  neurosphere formation and proliferation. In  Atm  −/−  neurosphere cells, the Akt and Erk1/2 pathways are disrupted, together with enhanced activity of the p38 mitogen‐activated protein kinase (MAPK). Treatment of these cells with the antioxidant  N ‐acetyl‐ L ‐cysteine (NAC) or with a p38 MAPK inhibitor restores normal proliferation and reduced expression of p21  cip1   and p27  kip1   in the  Atm  −/−  NSCs. These observations indicate that ATM plays a crucial role in NSC proliferation, by activating Akt and Erk1/2 pathways and by suppressing ROS‐p38 MAPK signaling. Together, our results suggest that p38 MAPK signaling acts as a negative regulator of NSC proliferation in response to oxidative stress. These findings suggest a potential mechanism for neuronal cell loss as a result of oxidative stress in NSCs in progressive neurodegenerative diseases such as A‐T. STEM CELLS 2009;27:1987–1998

Loss of ATM Impairs Proliferation of Neural Stem Cells Through Oxidative Stress‐Mediated p38 MAPK Signaling