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Do Wee Worms Hold the Key to Nerve Repair?

Axonal Fusion Process Could Someday Translate to Humans

Being able to automatically reconnect nerves after an injury may sound far-fetched. But the ability does exist––in microscopic roundworms. Several invertebrate species, including the Caenorhabditis elegans worm, can re-fuse and restore the function of severed neurons.

In a Journal of Neuroscience article published in April, researchers from the Queensland Brain Institute and Monash University detail how this process is regulated in a discovery that represents a step closer to translating this ability from worms to humans.

Neurons communicate via axons. In 2015, a team lead by one of the current study co-authors discovered C. elegans’ ability to execute axonal fusion, where two separated axons reconnect.

According to the researchers, instead of the injured nerves having to fully regrow so they can reconnect to the target, they simply bridge a gap to rejoin the nerve, allowing it to function once again.

To undergo axonal fusion, the axon still attached to the cell must first regrow, then position itself closely to its separated axonal fragment. After the two axons reconnect, they fuse their membranes to form a cohesive whole with an outer membrane and the inner material of the cell.

The process offers promise as a potential treatment for people with nerve injuries, which can cause life-long disabilities. However, investigating the molecular mechanisms underlying axonal fusion will be required first in order to understand the process.

The 2015 research focused on the EFF-1 molecule, which initiates the fusion process. This protein must be present at the nerve’s membrane to merge two axon fragments. If it is located within the cell, it is inactive.

The current researchers have discovered another key molecule in the process–the protein RAB-5. They found that RAB-5 plays a vital role in axonal fusion by regulating EFF-1. RAB-5, a trafficking protein, delivers other proteins from their site of manufacture in the cell to where they are needed. As RAB-5 controls the level of EFF-1 on the nerve membrane, this affects the nerve’s ability to repair itself.

The researchers are hopeful that one day, the fusion process will lead to being able to treat injuries such as paralysis in people.

Source: University of Queensland­–Queensland Brain Institute, April 30, 2019

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