Nucleolar stress characterized by downregulation of nucleophosmin: A novel cause of neuronal degeneration

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.