Roles of N-myc downstream-regulated gene 2 in the central nervous system: molecular basis and relevance to pathophysiology.

N-myc downstream-regulated gene 2 (NDRG2) is a member of the NDRG family, whose members have multiple functions in cell proliferation, differentiation, and stress responses. NDRG2 is widely distributed in the central nervous system and is uniquely expressed by astrocytes; however, its role in brain function remains elusive. The clinical relevance of NDRG2 and the molecular mechanisms in which it participates have been reported by studies using cultured cells and specimens of patients with neurological disorders. In recent years, genetic tools, including several lines of Ndrg2-knockout mice and virus-mediated gene transfer, have improved understanding of the roles of NDRG2 in vivo. This review aims to provide an update of recent growing in vivo evidence that NDRG2 is involved in brain function, focusing on research of Ndrg2-knockout mice with neurological disorders such as brain tumors, chronic neurodegenerative diseases, and acute brain insults including brain injury and cerebral stroke. These studies demonstrate that NDRG2 plays diverse roles in the regulation of astrocyte reactivity, blood-brain barrier integrity, and glutamate excitotoxicity. Further elucidation of the roles of NDRG2 and their molecular basis may provide novel therapeutic approaches for various neurological disorders.