Researchers find dozens of genes that block neuron regeneration

When cells in the central nervous system in the brain and spine are damaged by disease or injury, they fail to regenerate, limiting the body’s ability to recover. In contrast, the peripheral nerve cells that serve most other areas of the body are better able to regenerate. Scientists for decades have been looking for molecular clues as to why axons – the filiform projections that allow communication between cells of the central nervous system – cannot repair themselves after a stroke, spinal cord injury or traumatic brain injury.

On a huge screen of 400 mouse genes, the Yale School of Medicine researchers identified 40 genes actively involved in suppressing the regeneration of axons in cells of the central nervous system. By editing one of these genes, they were able to restore axons in the eye nerves of mice damaged by glaucoma.

The findings were published on March 2 in the newspaper Cell 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.

In the past few decades, Strittmatter and other scientists have discovered a handful of genes involved in suppressing the regeneration of cells in the central nervous system. But the advent of RNAs to silence gene expression and new gene-editing technologies capable of removing unique genes and assessing their functional impact has allowed researchers to greatly expand their search for other culprits.

Among the 400 candidate genes that Yale’s team previously identified in cultures of cortical neurons, they were able to show that one in 10 of these genes had a direct impact in vivo on the regeneration of axons in central nervous system cells in mice. One of the 40 edited genes encodes an immune system regulator known as interleukin-22. The elimination of this immune mediator altered the expression of many neuronal regeneration genes and greatly increased axon regeneration in mouse glaucoma models, they found.

Future research will explore how modifying or blocking these 40 genes can affect the repair of neurons damaged by stroke and traumatic brain and spinal cord injuries, said Strittmatter.