Deciphering the role of the cell cycle machinery in neuronal death and neurogenesis

Due to increasing life expectancy, the incidence of neurological disorders has increased over the past years. These neurological disorders, such as stroke, Alzheimer's Disease or Parkinson's Disease, are often associated with significant neuronal loss. Two strategies can be considered to counteract the loss of neurons: 1) to prevent neuronal death and 2) to replace lost neurons. Within this framework, the goal of our lab is to pinpoint molecular mechanisms regulating 1) neuronal death following stroke and 2) the production of new neurons from endogenous neural stem cells (NSC). We particularly focus our attention on the role of core cell cycle proteins, like cyclin-dependent kinases (Cdk), cyclins and Cdk inhibitors (Cdki) in these contexts. Using genetic and pharmacological approaches, we recently demonstrated that inhibition of Cdk1 is neuroprotective following stroke. We also showed that the Cdki p27kip1 supresses the production of new hippocampal neurons through inhibition of the kinase activity of Cdk6.