Rtn4r, also known as Nogo receptor 1 (NgR1), encodes a glycosylphosphatidylinositol-linked cell surface receptor with leucine-rich repeats. It is involved in regulating axonal growth, axon regeneration after injury [4,5]. RTN4R has been implicated in various biological processes, including neural development and repair, and is associated with pathways related to synaptic circuit formation, autophagy, and angiogenesis [1,2].

In genetic models, Rtn4r knockout mice have reduced ataxin-2 levels, suggesting it could be a novel therapeutic target for amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (SCA2) [3]. Knockdown of Rtn4 by siRNA in a study related to cerebral infarction led to reduced vascular autophagy and enhanced angiogenesis in the thalamus, along with rescued neuronal loss and improved cognitive function [2].

In conclusion, Rtn4r plays a crucial role in neural development and repair, influencing axonal growth and regeneration. Through gene-knockout models, its potential as a therapeutic target in neurodegenerative diseases like ALS and SCA2 has been revealed. Also, its role in regulating angiogenesis and autophagy after cerebral infarction has been demonstrated, highlighting its importance in understanding and potentially treating related neurological conditions.

References:

1. Wang, Jie, Miao, Yi, Wicklein, Rebecca, Garcia, K Christopher, Südhof, Thomas C. 2021. RTN4/NoGo-receptor binding to BAI adhesion-GPCRs regulates neuronal development. In Cell, 184, 5869-5885.e25. doi:10.1016/j.cell.2021.10.016. https://pubmed.ncbi.nlm.nih.gov/34758294/

2. Xiao, Peiyi, Gu, Jinmin, Xu, Wei, Zeng, Jinsheng, Xing, Shihui. 2022. RTN4/Nogo-A-S1PR2 negatively regulates angiogenesis and secondary neural repair through enhancing vascular autophagy in the thalamus after cerebral cortical infarction. In Autophagy, 18, 2711-2730. doi:10.1080/15548627.2022.2047344. https://pubmed.ncbi.nlm.nih.gov/35263212/

3. Rodriguez, Caitlin M, Bechek, Sophia C, Jones, Graham L, Strittmatter, Stephen M, Gitler, Aaron D. . Targeting RTN4/NoGo-Receptor reduces levels of ALS protein ataxin-2. In Cell reports, 41, 111505. doi:10.1016/j.celrep.2022.111505. https://pubmed.ncbi.nlm.nih.gov/36288715/

4. Hsu, Ruby, Woodroffe, Abigail, Lai, Wen-Sung, Karayiorgou, Maria, Gogos, Joseph A. 2007. Nogo Receptor 1 (RTN4R) as a candidate gene for schizophrenia: analysis using human and mouse genetic approaches. In PloS one, 2, e1234. doi:. https://pubmed.ncbi.nlm.nih.gov/18043741/

5. Lazar, Noah L, Singh, Shiva, Paton, Tara, Roder, John C, Cain, Donald P. 2011. Missense mutation of the reticulon-4 receptor alters spatial memory and social interaction in mice. In Behavioural brain research, 224, 73-9. doi:10.1016/j.bbr.2011.05.020. https://pubmed.ncbi.nlm.nih.gov/21645550/