E3 ubiquitin ligase Nedd4-2 exerts neuroprotective effects during endoplasmic reticulum stress

Lodes DE, Zhu J, and Tsai N-P.

Journal of Neurochemistry, 2021.


Scientists use Axion’s Maestro platform to explore the potential role of Nedd4-2 in neurological disease

Nedd4-2 (neural precursor cell expressed developmentally downregulated protein 4-like) is an E3 ubiquitin ligase that is essential for neurodevelopment and homeostasis of neural circuit excitability. Studies have established that Nedd4.2 is associated with a number of diseases including hypertension, epilepsy, and cystic fibrosis via the dysregulation of specific proteins, but emerging research shows that cellular stress may also play a role in the activation and regulation of Nedd4-2. In this study, researchers conduct biochemical and physiological experiments to investigate if Nedd4-2 offers neuroprotection during endoplasmic reticulum (ER) stress.

To explore neural network activity in Nedd4-2 knockout mice, the researchers used Axion’s Maestro multielectrode array (MEA) platform and found Nedd4-2 is needed for maintaining spontaneous neural activity and excitatory synapses following the induction of ER stress. Other testing supported the important role of Nedd4-2 in mediating the cellular response to ER. Overall, the authors suggest that the findings may provide greater insight into the pathogenesis of neurological diseases.