AI Article Synopsis
- Researchers are exploring gene-based therapies to reduce ataxin-2 levels for treating neurodegenerative diseases like ALS and SCA2.
- A genome-wide study identified the RTN4R gene, which influences ataxin-2 levels, and demonstrated that targeting this gene can effectively lower ataxin-2 in both human and mouse neurons.
- The findings suggest that targeting the RTN4/NoGo-Receptor could be a new treatment strategy for ALS and SCA2, as reducing either RTN4 or ataxin-2 promotes better axonal regeneration after nerve injury.
Article Abstract
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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9664481 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2022.111505 | DOI Listing |
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