Nrn1, also known as Neuritin 1, is a neurotrophic factor crucial for neurodevelopment and synaptic plasticity. It is involved in neural cell survival, differentiation, axonal and dendritic growth, as well as synapse formation and maturation. The expression of Nrn1 can be enhanced by BDNF, and it is suggested to activate the insulin receptor (IR) pathway to promote the transcription of CACNA1C [3]. Nrn1 has been associated with multiple biological processes and diseases, highlighting its overall biological importance.

In melanoma, Nrn1 was found to interact directly with the cleaved intracellular domain of Notch1 and Notch3, reducing the expression of Hes1, which in turn affects the sequestration of JAK and STAT3 in a phosphorylation complex, ultimately influencing the oncogenic STAT3 signaling [1].

In schizophrenia, genetic and neuroimaging approaches have shown an association between Nrn1 and early-onset schizophrenia. Different haplotypes of Nrn1 were associated with early-onset, and its genetic epistasis with BDNF and CACNA1C affected the clinical presentation of the disorder via neuroanatomical changes [2,3].

In optic nerve crush rats, Nrn1 overexpression attenuated retinal ganglion cell apoptosis, promoted axonal regeneration, and improved visual function by activating the Akt1 and Stat3 pathways and inhibiting the mitochondrial apoptotic pathway [4].

In esophageal cancer, Nrn1 suppresses cancer growth both in vitro and in vivo by inhibiting PI3K-Akt-mTOR signaling, and its methylation is a novel synthetic lethal marker for related inhibitors [5].

In diacetylmorphine-induced neuronal apoptosis, NEFL was found to regulate the Nrn1-mediated mitochondrial pathway to promote apoptosis [6]. Also, in schizophrenia, NRN1 genetic variability and methylation changes may serve as biomarkers for cognitive remediation therapy response [7].

And in Alzheimer's disease, NRN1 provided dendritic spine resilience against amyloid-β and blocked amyloid-β-induced neuronal hyperexcitability in cultured neurons [8].

In conclusion, Nrn1 plays essential roles in neural-related biological processes, including neural cell survival, synapse formation, and synaptic plasticity. Through model-based research, its significance in various disease areas such as melanoma, schizophrenia, optic nerve injury, esophageal cancer, drug-induced neuronal apoptosis, and Alzheimer's disease has been revealed. These findings contribute to a better understanding of the underlying mechanisms of these diseases and may provide potential therapeutic targets.