2008 Brain Star Award Recipient - Yasmilde Rodriguez Gonzalez
Recipient
Yasmilde Rodriguez Gonzalez - Biosketch
PhD Neuroscience
University of Ottawa
Article
CITED2 signals through peroxisome proliferator-activated receptor-gamma to regulate death of cortical neurons after DNA damage. Gonzalez YR, Zhang Y, Behzadpoor D, Cregan S, Bamforth S, Slack RS, Park DS. Journal of Neuroscience; 28(21):5559-69; 2008.
Significance of the paper
The results reported on this paper define a novel neuronal prodeath pathway in which Cdk4-mediated regulation of Cited2 activates PPARgamma and consequently caspase. This is the first time that any role of Cited2 in neurodegeneration is reported. We not only showed that PPARgamma is a Cited2 direct target to promote apoptosis but that other Cited2 targets (e.i HIF) that are relevant to other tissues (heart) are not involved in Cited2-induced neuronal apoptosis. We showed as well that Cdk4 activity is responsible for Cited2 regulation after DNA damage. This appears to be a Cdk4-induced pathway that could be independent of the already known Rb-E2F pathway.
These findings enrich our understanding of how neurons undergo apoptosis after DNA Damage, a process that is part of neurodegerative conditions such as Parkinson's disease and Stroke. As such, they will contribute to the development of new therapeutic methodologies as well as to our awareness as to how to evaluate them. Additionally, this paper provides the first functional data regarding a neuronal Cited2 target, which could facilitate studies as to how Cited2 mutations lead to risk for Spina Bifida in humans.