Cyclin’s Role in Parkinson’s Disease
Our collaborative efforts with the Sicinski and Moss labs (Odajima et al., 2011) uncovered that Cyclin E, a core cell cycle machinery protein, plays a role in the postmitotic adult nervous system where it promotes synaptic growth and function through inhibiting the atypical Cdk, Cdk5. Interestingly, Cyclin E is a target ubiquitin-mediated degradation via the E3 ligase, Parkin, one of the genes most highly mutated in autosomal recessive forms of Parkinson’s disease (Starpoli et al., 2003; Veeriah et al., 2010). Further, Cyclin E appears to be upregulated in PD, suggesting Cyclin E overexpression may contribute to disease pathology. We propose to test this hypothesis by studying the function of Cyclin E in the Nigra-striatal circuit (Fig. 5).