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However, whether ASPP1\/2 play a role in the regulation of p53-dependent neuronal death in the CNS is currently unknown. To address this, we asked whether ASPP1\/2 contribute to the death of retinal ganglion cells (RGCs) using<jats:italic>in vivo<\/jats:italic>models of acute optic nerve damage in mice and rats. Here, we show that p53 is activated in RGCs soon after injury and that axotomy-induced RGC death is attenuated in p53 heterozygote and null mice. We demonstrate that ASPP1\/2 proteins are abundantly expressed by injured RGCs, and that short interfering (si)RNA-based ASPP1 or ASPP2 knockdown promotes robust RGC survival. Comparative gene expression analysis revealed that siASPP-mediated downregulation of p53-upregulated-modulator-of-apoptosis (PUMA), Fas\/CD95, and Noxa depends on p53 transcriptional activity. Furthermore, siRNA against PUMA or Fas\/CD95 confers neuroprotection, demonstrating a functional role for these p53 targets in RGC death. Our study demonstrates a novel role for ASPP1 and ASPP2 in the death of RGCs and provides evidence that blockade of the ASPP\u2013p53 pathway is beneficial for central neuron survival after axonal injury.<\/jats:p>","DOI":"10.1523\/jneurosci.2635-12.2013","type":"journal-article","created":{"date-parts":[[2013,1,30]],"date-time":"2013-01-30T18:05:15Z","timestamp":1359569115000},"page":"2205-2216","source":"Crossref","is-referenced-by-count":45,"title":["ASPP1\/2 Regulate p53-Dependent Death of Retinal Ganglion Cells through PUMA and Fas\/CD95 Activation<i>In Vivo<\/i>"],"prefix":"10.1523","volume":"33","author":[{"given":"Ariel 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