NRG3, short for Neuregulin 3, is a ligand of ERBB4, and they are part of a signaling network. This network is involved in various biological processes, including neuronal function, mammary gland development, and cell growth regulation [2,3]. In neurons, NRG3 processing and sorting are crucial for its function, and it accumulates at presynaptic terminals through trans-synaptic retention with postsynaptic ErbB4 [5].

In terms of disease-related findings, in chronic schizophrenia patients, the NRG3 rs10748842 polymorphism may not confer susceptibility to schizophrenia but is associated with cognitive deficits, especially in attention performance [1]. In canine glioma, the NRG3/ERBB4 signaling cascade is negatively regulated by miR-190a and contributes to cell growth, suggesting it as a potential therapeutic target [2]. In Alzheimer's disease, genetic variants in the NRG3 gene are associated with the risk and age at onset of the disease [4]. In nicotine withdrawal, the NRG3-ERBB4 signaling pathway in the ventral hippocampus contributes to anxiety-related behaviors [6]. Also, denervation-induced NRG3 aggravates muscle heterotopic ossification via the ErbB4/PI3K/Akt signaling pathway [7].

In conclusion, NRG3 plays essential roles in multiple biological processes and is implicated in various disease conditions. Studies on NRG3, especially through genetic models, have provided insights into its functions in schizophrenia, Alzheimer's disease, canine glioma, nicotine withdrawal-related behaviors, and muscle heterotopic ossification, which may help in developing potential therapeutic strategies for these conditions.

References:

1. Li, Zezhi, Liu, Lihua, Lin, Wei, Tang, Wei, Zhang, Xiangyang. 2019. NRG3 contributes to cognitive deficits in chronic patients with schizophrenia. In Schizophrenia research, 215, 134-139. doi:10.1016/j.schres.2019.10.060. https://pubmed.ncbi.nlm.nih.gov/31753594/

2. Noguchi, Shunsuke, Inoue, Marina, Ichikawa, Tomotsugu, Akiyoshi, Hideo, Kamishina, Hiroaki. 2021. The NRG3/ERBB4 signaling cascade as a novel therapeutic target for canine glioma. In Experimental cell research, 400, 112504. doi:10.1016/j.yexcr.2021.112504. https://pubmed.ncbi.nlm.nih.gov/33508276/

3. Howard, Beatrice A. 2008. The role of NRG3 in mammary development. In Journal of mammary gland biology and neoplasia, 13, 195-203. doi:10.1007/s10911-008-9082-8. https://pubmed.ncbi.nlm.nih.gov/18418701/

4. Wang, Ke-Sheng, Xu, Nuo, Wang, Liang, Escamilla, Michael A, Xu, Chun. 2013. NRG3 gene is associated with the risk and age at onset of Alzheimer disease. In Journal of neural transmission (Vienna, Austria : 1996), 121, 183-92. doi:10.1007/s00702-013-1091-0. https://pubmed.ncbi.nlm.nih.gov/24061483/

5. Ahmad, Tanveer, Vullhorst, Detlef, Chaudhuri, Rituparna, Bonifacino, Juan S, Buonanno, Andres. 2022. Transcytosis and trans-synaptic retention by postsynaptic ErbB4 underlie axonal accumulation of NRG3. In The Journal of cell biology, 221, . doi:10.1083/jcb.202110167. https://pubmed.ncbi.nlm.nih.gov/35579602/

6. Fisher, Miranda L, Prantzalos, Emily R, O'Donovan, Bernadette, Ortinski, Pavel I, Turner, Jill R. 2023. Dynamic Effects of Ventral Hippocampal NRG3/ERBB4 Signaling on Nicotine Withdrawal-Induced Responses. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.01.17.524432. https://pubmed.ncbi.nlm.nih.gov/36711798/

7. Ma, Lin, Kang, Xia, Tan, Jindong, Tang, Kanglai, Bian, Xuting. 2024. Denervation‑induced NRG3 aggravates muscle heterotopic ossification via the ErbB4/PI3K/Akt signaling pathway. In Molecular medicine reports, 31, . doi:10.3892/mmr.2024.13374. https://pubmed.ncbi.nlm.nih.gov/39450542/