Regenerating rat neurons. Image credit: Dong Wang (CC BY 4.0).
Nerve cells, or neurons, are the key communication components of the body. Each neuron takes signals from many inputs and transmits them through a single output called the axon. In the central nervous system, which consists of the brain and spinal cord, damaged neurons do not generally repair themselves. But in the peripheral nervous system, where neurons branch out to other parts of the body, they can regenerate. For this to happen, genes which promote axon regrowth must be expressed.
Messenger RNA carries DNA information from the nucleus of a cell to the cytoplasm where it serves as instructions for generating proteins. Certain enzymes can modify messenger RNA, changing how long it lasts, where it goes in the cell and what proteins it makes. It has been suggested that a particular RNA modification, known as m6A, plays an important role in axon regrowth as increased m6A levels have been reported in some neurons after a peripheral nerve injury.
Wang et al. studied the impact of m6A modifications on axon regrowth by examining the effects of several genes associated with these modifications in rats. The experiments showed that expression of a gene called Alkbh5 – which codes for an enzyme that removes m6A modifications – regulates the amount of axon regrowth following an injury to peripheral nerves. Reducing the amount of Alkbh5 expression rates increased axon regrowth, whereas in rats where Alkbh5 was overexpressed, regrowth was reduced. Further experiments showed that the ALKBH5 enzyme helps to make mRNA from the gene Lpin2 more stable, which affects how it processes fats and lipids during the regeneration process. Moreover, in the central nervous system, reducing Alkbh5 expression enhanced survival and axon regrowth of neurons in the eye after they were injured in mice.
The findings suggest that Alkbh5 influences axon regrowth and are an important step towards understanding how biological systems repair nerve damage. Future work should investigate if stopping Alkbh5 expression allows injured neurons to recover their function and how different m6A-associated enzymes work together in this process.
