| First Author | Rodriguez CM | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 4 | Pages | 111505 |
| PubMed ID | 36288715 | Mgi Jnum | J:331546 |
| Mgi Id | MGI:7380182 | Doi | 10.1016/j.celrep.2022.111505 |
| Citation | Rodriguez CM, et al. (2022) Targeting RTN4/NoGo-Receptor reduces levels of ALS protein ataxin-2. Cell Rep 41(4):111505 |
| abstractText | Gene-based therapeutic strategies to lower ataxin-2 levels are emerging for the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (SCA2). Additional strategies to lower levels of ataxin-2 could be beneficial. Here, we perform a genome-wide arrayed small interfering RNA (siRNA) screen in human cells and identify RTN4R, the gene encoding the RTN4/NoGo-Receptor, as a potent modifier of ataxin-2 levels. RTN4R knockdown, or treatment with a peptide inhibitor, is sufficient to lower ataxin-2 protein levels in mouse and human neurons in vitro, and Rtn4r knockout mice have reduced ataxin-2 levels in vivo. We provide evidence that ataxin-2 shares a role with the RTN4/NoGo-Receptor in limiting axonal regeneration. Reduction of either protein increases axonal regrowth following axotomy. These data define the RTN4/NoGo-Receptor as a novel therapeutic target for ALS and SCA2 and implicate the targeting of ataxin-2 as a potential treatment following nerve injury. |
