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Sci Rep. 2016 Apr 12;6:24279. doi: 10.1038/srep24279.

Cell-permeable p38 MAP kinase promotes migration of adult neural stem/progenitor cells.

Author information

1
Department of Physiology, Toho University School of Medicine, 143-8540, Tokyo, Japan.
2
Advanced Medical Research Center, Toho University Graduate School of Medicine, Tokyo 143-8540, Japan.
3
Brain and Spinal Injury Center (BASIC), Department of Neurological Surgery, University of California, San Francisco, 94110, California, USA.
4
Research Team for Mechanism of Aging, Redox Research, Tokyo Metropolitan Institute of Gerontology, 173-0015, Tokyo, Japan.
5
Department of Neurochemistry, National Institute of Neuroscience, 187-8502, Tokyo, Japan.
6
Department of Pathology, Toho University School of Medicine, 143-8540, Tokyo, Japan.
7
Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, 359-8555, Saitama, Japan.

Abstract

Endogenous neural stem/progenitor cells (NPCs) can migrate toward sites of injury, but the migration activity of NPCs is insufficient to regenerate damaged brain tissue. In this study, we showed that p38 MAP kinase (p38) is expressed in doublecortin-positive adult NPCs. Experiments using the p38 inhibitor SB203580 revealed that endogenous p38 participates in NPC migration. To enhance NPC migration, we generated a cell-permeable wild-type p38 protein (PTD-p38WT) in which the HIV protein transduction domain (PTD) was fused to the N-terminus of p38. Treatment with PTD-p38WT significantly promoted the random migration of adult NPCs without affecting cell survival or differentiation; this effect depended on the cell permeability and kinase activity of the fusion protein. These findings indicate that PTD-p38WT is a novel and useful tool for unraveling the roles of p38, and that this protein provides a reasonable approach for regenerating the injured brain by enhancing NPC migration.

PMID:
27067799
PMCID:
PMC4828673
DOI:
10.1038/srep24279
[Indexed for MEDLINE]
Free PMC Article

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