Signaling Cascade That Repairs Damaged Nerve Cells Characterized

Source: Nagoya University

Summary: Researchers showed that a signaling cascade that normally functions in promoting the phagocytosis of apoptotic cells also acts in inducing axon regeneration.

Through a study of roundworm nerve cells with severed axons, researchers have identified the series of molecules involved in the regeneration of damaged nerves in them, showing that it largely overlaps with the signals used by the intrinsic removal system to take up and process dying cells. The branches of nerve cells called axons are particularly susceptible to damage due to the long distances they extend to communicate with each other. In humans, such damage in peripheral regions of the body can be relatively well repaired, but this repair is less effective in the brain and the spinal cord, which helps to explain why conditions such as brain and spinal cord injuries are so debilitating. Researchers from the Nagoya University showed that a signaling cascade that normally functions in promoting the phagocytosis of apoptotic cells also acts in inducing axon regeneration. The study findings were published in the journal Nature Communications.

Series of signals

Credit: Nagoya University

The team used a laser to cut roundworm axons and then analyzed the subsequent series of molecular reactions that occurred. They found that this damage resulted in the movement of a lipid called phosphatidylserine (PS) from the inside of cells to their outside, which was mediated by a protein called an ABC transporter. This externalized PS was then recognized by another molecule, triggering a series of reactions that eventually led to repair of the axon. Interestingly, PS is better known as an “eat me” signal that helps the phagocytosis of a dying cell by its neighbors. The team explains that for the repair of damaged nerves, the PS labeling appears only at the severed sites and exists for only a short time(~1 hr), which is in contrast to the labeling in eliminating dying cells that remains for a long time until the cells are eliminated.

According to Naoki Hisamoto, “Now that we know how this system works in the relatively simple roundworm, we should eventually be able to extrapolate the findings to humans. This could provide us with a range of targets for pharmaceutical interventions to treat conditions like brain and spinal cord injuries, in which the human body is not able to repair damaged nerves.”

More Information: Naoki Hisamoto et al, “Phosphatidylserine exposure mediated by ABC transporter activates the integrin signaling pathway promoting axon regeneration”, Nature Communications (2018). DOI: 10.1038/s41467-018-05478-w

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