Sheldrick, Melissa Lynn2013-11-072013-11-0720082008Source: Masters Abstracts International, Volume: 48-01, page: 0308.http://hdl.handle.net/10393/28024http://dx.doi.org/10.20381/ruor-12350Elucidation of molecular mechanisms modulating the death and failure of neurons to regenerate after cerebral ischemia is important in developing therapeutics to stroke. Here, results demonstrate that the pro-death transcription factor E2F1 inhibits neuronal survival through up-regulation of the receptor for axon repulsive guidance molecule, NRP-1. First, NRP-1 is shown as a direct target of E2F1 based on: reactivation of NRP-1 expression in E2F1-/- neurons after E2F1 replacement, EMSA and reporter assays confirming E2F1 binding and activation of the NRP-1 promoter, respectively. Second, pharmacological and genetic inhibition of NRP-1 conferred neuroprotection. Collectively, these findings support a model in which E2F1 targets NRP1 to modulate axonal damage and neuronal death in response to cerebral ischemia. Future work should determine the differential contributions of NRP-1 and NRP-2 in neuronal survival. Studies in vivo will also confirm the therapeutic benefit of inhibition of NRPs in stroke recovery.132 p.enBiology, Neuroscience.Thesis