N-Myc downstream-regulated gene 4 protein (NDRG4)

N-Myc downstream-regulated gene 4 protein (NDRG4) is an intracellular protein belonging to the alpha/beta hydrolase superfamily, highly expressed in the brain and heart, and involved in cell proliferation, regulation of apoptosis, neuronal survival, and vascular smooth muscle cell function[1][2][3][6]. NDRG4 maintains intracerebral BDNF levels, is necessary for spatial learning and resistance to ischemic stress, and promotes cell survival in astrocytes and neuronal cells[4][6]. In cancer, NDRG4 can act as either a tumor suppressor (colorectal cancer) or oncogenic factor (aggressive meningioma, glioblastoma), regulating apoptosis via the p53-BAX-Bcl-2 pathway and affecting cell cycle progression, migration, and angiogenesis[1]. NDRG4 is under investigation as a molecular target for gene therapy in malignant meningiomas and serves as a biomarker for disease progression in several tumor types[1].

Other names

Protein NDRG4BDM1KIAA1180SMAP-8Brain development-related molecule 1Vascular smooth muscle cell-associated protein 8Smooth muscle-associated protein 8

No approved small molecules directly targeting NDRG4, but RNA interference (shRNA) against NDRG4 induces mitochondrial-mediated apoptosis and reduces proliferation in meningioma cells[1] Targeting NDRG4 alters p53 phosphorylation, BAX/Bcl-2 pathway, and mitochondrial membrane potential, leading to caspase-mediated apoptosis[1]