Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1930154 | Biochemical and Biophysical Research Communications | 2012 | 7 Pages |
Nucleophosmin (NPM) is a multifunctional nucleolar protein that has been linked with nucleolar stress. In non-neuronal cell lines, NPM may enhance or inhibit the activity of tumor suppressor p53, a major apoptotic protein. The relationship between NPM and p53 in the central nervous system (CNS) remains unknown. Here, we assessed the role of NPM in the CNS using a model of seizure-induced neurodegeneration. We show that NPM overexpression is neuroprotective against kainic acid-induced excitotoxicity, and that downregulation of NPM is pro-apoptotic in a p53-independent manner. These results suggest a key role for NPM in promoting neuronal survival and a novel mechanism of neuronal degeneration triggered by nucleolar stress.
► Kainic acid-induced excitotoxicity downregulates nucleophosmin in the central nervous system. ► Downregulation of nucleophosmin is associated with neuronal cell death in a p53-independent manner. ► Restoration of nucleophosmin level in the central nervous system is neuroprotective.