Neuritin (Nrn1) is a neurotrophin that plays an important role in nervous system plasticity and repair following nerve injury. MicroRNAs (miRNAs) are a type of small non‐coding RNA that regulate nearly all aspects of nerve development and survival, including apoptosis. Here it was found that miR‐204 negatively regulates Nrn1 protein expression through direct interaction with Nrn1 transcript. Moreover, miR‐204 activates cleaved caspase‐3, enhancing the sensitivity of RSC96 Schwann cells to H₂O₂‐induced oxidative stress and apoptosis. Thus, miR‐204 expressed at a low level may create a microenvironment suitable for the repair of injured nerves by relieving the inhibition of Nrn1 transcription and stimulating the anti‐apoptotic function of Schwann cells. These results provide novel insights into the roles of miR‐204 in nerve injury and repair.

Neuritin plays an important role in neural development and plasticity. A recent study demonstrated that increasing Neuritin levels attenuated synaptic damage in mice with Alzheimer's disease (AD), which exhibit a decreased Neuritin expression. However, it remains unclear as to whether Neuritin expression is regulated by microRNAs (miRNAs or miRs) in AD. In the present study, it was found that miR‑199a decreased Neuritin expression and was therefore involved in the development of AD. Subsequently, differentially expressed miRNAs in AD from datasets and the literature were recruited, and those that could bind Neuritin were predicted using bioinformatics analysis. The present study then focused on the candidate miRNAs that were highly associated with Neuritin and were upregulated in AD. The expression patterns of the candidate miRNAs and Neuritin in the hippocampus and cortex of APP/PS1 (AD model) mice at different stages were then detected and analyzed. It was found that miR‑199a expression was significantly increased in the early stages of AD and was negatively associated with Neuritin expression. Furthermore, it was revealed that the decreased Neuritin expression was due to the direct targeting of the Neuritin 3'‑UTR by miR‑199a. Finally, the association between the spatial memory capacity of APP/PS1 mice and the changes in miR‑199a and Neuritin expression protein was investigated. On the whole, the data of the present study suggest that miR‑199a is involved in the development of AD by regulating Neuritin expression.

Neuritin plays a key role in neural development and regeneration by promoting neurite outgrowth and synapse maturation. However, the mechanism of neuritin in modulating neurite growth has not been elucidated. Here, using yeast two-hybrid we screened and discovered the interaction of neuritin and neuralized (NEURL1), which is an important regulator that can activate Notch signaling through promoting endocytosis of Notch ligand. And then we identified the interaction of neuritin and neuralized by co-immunoprecipitation (IP) assays, and clarified that neuritin and NEURL1 were co-localized on the cell membrane of SH-SY5Y cells. Moreover, neuritin significantly suppressed Notch ligand Jagged1 (JAG1) endocytosis promoted by NEURL1, and then inhibited the activation of Notch receptor NICD and decreased the expression of downstream gene HES1. Importantly, the effect of neuritin on inhibiting Notch signaling was rescued by NEURL1, which indicated that neuritin is an upstream and negative regulator of NEURL1 to inhibit Notch signaling through interacted with NEURL1. Notably, recombinant neuritin restored the retraction of neurites caused by activation of Notch, and neurite growth stimulated by neuritin was partially blocked by NEURL1. These findings establish neuritin as an upstream and negative regulator of NEURL1 that inhibits Notch signaling to promote neurite growth. This mechanism connects neuritin with Notch signaling, and provides a valuable foundation for further investigation of neuritin’s role in neurodevelopment and neural plasticity.

Neuritin is a new neurotropic factor implicated in nervous system development and plasticity. Studies have shown that Neuritin is upregulated in injured nerves, suggesting that it is involved in nerve repair. To test this hypothesis, we investigated whether recombinant human Neuritin could restore nerve structure and function in a rat model of sciatic nerve injury. Neuritin treatment had a dose-dependent effect on functional recovery 4 weeks after injury, as determined by the walking-track test. Similar trends were observed for gastrocnemius muscular strength and nerve conduction velocity. Additionally, sciatic nerve fiber density and organization as well as degree of remyelination were increased, while growth-associated protein 43 and neurofilament 200 expression was upregulated upon treatment with Neuritin. These findings demonstrate that Neuritin stimulates nerve regeneration and functional recovery and thus promotes the repair of injured sciatic nerves.