Abstract
Signaling from the synapse to nucleus is mediated by the integration and propagation of both membrane potential changes (postsynaptic potentials) and intracellular second messenger cascades. The electrical propagation of postsynaptic potentials allows for rapid neural information processing, while propagating second messenger pathways link synaptic activity to the transcription of genes required for neuronal survival and adaptive changes (plasticity) underlying circuit formation and learning. The propagation of activity-induced calcium signals to the cell nucleus is a major synapse-to-nucleus communication pathway. Neuronal PAS domain protein 4 (Npas4) is a recently discovered calcium-dependent transcription factor that regulates the activation of genes involved in the homeostatic regulation of excitatory–inhibitory balance, which is critical for neural circuit formation, function, and ongoing plasticity, as well as for defense against diseases such as epilepsy. Here, we summarize recent findings on the neuroprotective functions of Npas4 and the potential of Npas4 as a therapeutic target for the treatment of acute and chronic diseases of the central nervous system.
Highlights
Many adaptive changes in brain function such as learning depend on the capacity of individual neurons to transduce changes in postsynaptic membrane potential into longer-lasting changes in gene transcription, leading to stable biochemical and structural modifications (Fernandez-Albert et al, 2019)
Neuronal PAS domain protein 4 (Npas4) is a recently discovered calcium-dependent transcription factor that regulates the activation of genes involved in the homeostatic regulation of excitatory–inhibitory balance, which is critical for neural circuit formation, function, and ongoing plasticity, as well as for defense against diseases such as epilepsy
Given that Npas4 possesses a unique arrangement of localization signals (Greb-Markiewicz et al, 2018) and has been implicated in neuroprotection against various form of stress, elucidating the factors driving neuron-specific expression in hippocampus, cortex, striatum, midbrain (Drgonova et al, 2016), amygdale (Ji et al, 2019; Cerqueira et al, 2020), and nucleus accumbens (NAc) (Taniguchi et al, 2017; Funahashi et al, 2019) may identify new therapeutic strategies for a host of central nervous system diseases
Summary
Many adaptive changes in brain function such as learning depend on the capacity of individual neurons to transduce changes in postsynaptic membrane potential into longer-lasting changes in gene transcription, leading to stable biochemical and structural modifications (termed neural plasticity) (Fernandez-Albert et al, 2019). Neuronal PAS domain protein 4 (Npas4) is a recently discovered calcium-dependent transcription factor that regulates the activation of genes involved in the homeostatic regulation of excitatory–inhibitory balance, which is critical for neural circuit formation, function, and ongoing plasticity, as well as for defense against diseases such as epilepsy.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call