Ndrg2-flox Mouse

Ndrg2, a member of the N-myc downstream-regulated gene (NDRG) family, is principally expressed in astrocytes of the central nervous system. It is involved in cell proliferation and differentiation and is commonly regarded as a tumor suppressor. Ndrg2 affects multiple cellular processes such as apoptosis, astrogliosis, blood-brain barrier integrity, and glutamate clearance, and is associated with pathways like NF-κB/C3, Wnt/β-catenin, and interactions with proteins like PPM1A [4].

In the context of diabetes-associated cognitive dysfunction, Ndrg2 deficiency in astrocytes aggravated the activation of complement C3 by accelerating the phosphorylation of NF-κB, leading to synaptic injury and cognitive dysfunction. Conversely, overexpression of Ndrg2 promoted astrocytic remodeling by inhibiting complement C3, attenuating synaptic injury and cognitive dysfunction [1].

In the case of blood-brain barrier disruption after subarachnoid hemorrhage, Ndrg2 knockout in astrocytes inhibited MMP-9 expression and attenuated BBB damage, as cytoplasmic Ndrg2 bound to PPM1A and restricted the dephosphorylation of Smad2/3 [2].

In oxygen-glucose deprivation conditions, Ndrg2 inhibition in astrocytes increased inflammation and upregulated immune-associated genes and signaling pathways [3].

For ischemic stroke, Ndrg2 overexpression in astrocytes treated with oxygen-glucose deprivation/reoxygenation (OGD/R) aggravated the loss of glucose metabolism and promoted ferroptosis through inhibiting Wnt/β-catenin signaling activation [5].

In conclusion, Ndrg2 plays essential roles in maintaining normal brain function, especially in astrocyte-related processes. Studies using Ndrg2 knockout or conditional knockout mouse models have revealed its significance in diseases such as diabetes-associated cognitive dysfunction, subarachnoid hemorrhage-induced BBB disruption, cerebral ischemia, and ischemic stroke, highlighting its potential as a therapeutic target for these neurological conditions.