Cell-permeable p38 MAP kinase protects adult hippocampal neurons from cell death

Abstract

p38 mitogen-activated protein (MAP) kinase (p38) is a member of the MAP kinase family. Previous reports using p38 chemical inhibitors have suggested that its activation contributes to hippocampal neuronal cell death rather than cell survival. In this study, we used both a cell-permeable p38 protein containing the HIV protein transduction domain (PTD) and cultured adult hippocampal neurons, which were differentiated from cultured adult hippocampal neural stem/progenitor cells (NPCs), to evaluate the direct function of p38 on adult hippocampal neurons. Our immunocytochemical experiments demonstrated that wild-type cell-permeable p38 protein prevents cell death of adult hippocampal neurons induced by a low glucose condition. Our findings indicate that cell-permeable p38 protein may be useful in preventing the degeneration of higher brain function occurring through hippocampal neuronal cell death, and furthermore, that the maintenance of intracellular p38 levels could be another therapeutic target for neurodegenerative diseases such as Alzheimer's disease (AD).