Researchers find dozens of genes blocking neuronal regeneration

If the central nervous system in the brain and spine is damaged by disease or injury, it does not repair, which limits the body’s ability to recover. In contrast, peripheral nerve cells that serve most other parts of the body can regenerate more. Scientists have been searching for decades for molecular clues as to why axons – the filamentous projections that enable communication between central nervous systems – cannot recover themselves after stroke, spinal cord damage or traumatic brain injury.

In a massive screen of 400 mouse genes, researchers from Yale School of Medicine identified 40 genes that are actively involved in the suppression of axon regeneration in the central nervous system. By editing one of the genes, they were able to restore axons in the eye nerves of mice damaged by glaucoma.

The findings will be reported in the journal on March 2. Self-reports.

“This opens a new chapter in regeneration research,” said Stephen Strittmatter, Vincent Coates’ professor of neurology and professor of neuroscience and senior author of the study.

Over the past few decades, Strittmatter and other scientists have found a handful of genes involved in suppressing the rebirth of cells in the central nervous system. But the advent of RNAs to silence gene expression and new gene-editing technologies that can remove single genes and measure their functional impact has enabled researchers to greatly expand their search for other culprits.

Among the 400 candidate genes that the Yale team had previously identified in cultures of cortical neurons, they were able to show that one in ten of those genes had a direct in vivo impact on axon regeneration in central nervous system cells in mice. One of the 40 genes edited encodes an immune system regulator known as interleukin-22. The elimination of this immune mediator altered the expression of many neuronal regeneration genes and significantly increased axon regeneration in mouse models of glaucoma.

Future research will investigate the modification or blocking of the 40 genes that may affect the repair of neurons damaged by stroke and traumatic brain and spinal cord injuries, Strittmatter said.