A new signaling pathway could illuminate the repair of damage during brain injury

Most human cells are able to repair damage by dividing into wounds.

But the mature nerve cells (neurons) in our brain are different. If they try to split, they will probably die, and this is what happens during a brain injury or in conditions like Alzheimer’s disease (AD). Now, new research led by the University of Plymouth has uncovered a path that has shed new light on how these divisions can be triggered.

The research, published today in Cell Reports, has focused on intracellular structures called microtubules, which are found in most animal cells, and can be damaged by the buildup of a protein called Tau in the brain during illness.

The study was conducted in fruit flies, compared with postmortem brain samples from patients with AD.

The paper shows that when the microtubules in the neuronal cells of fruit flies are damaged, division is activated by activating the small signaling kinases, Tak1 and Ik2. Surprisingly, activation of these molecules can also be seen in the brains of the disease.

Why is it important?

By understanding the behavior of damaged microtubules, scientists have a valuable opportunity to potentially prevent neuronal death. brain injury, or after neurodegeneration, as in Alzheimer’s disease.

The research was conducted on fruit flies, but the team tested the applicability of its results by making fly neuronal cells express human Tau and also examine humans post mortem. brain samples from patients with EA.

An abnormal human Tau destroys the brain microtubules of flies and Alzheimer’s and, interestingly, can cause the same signaling cascade that was discovered in the fly’s neuron. cells after microtubules damage.

The researchers also found that higher levels of Tau accumulation correlated with a higher frequency of splitting neurons and neuronal death, but have not yet established any direct link or cause.

What should happen next?

The work was carried out at the Plymouth Institute for Health and Care Research (PIHR) and was led by Dr Torsten Bossing.

He said of current research and future plans: “As other scientists explore Tau and how it accumulates, we are studying more thoroughly what happens to the cell after it has been damaged.

“The fact that the two identified signaling kinases are next to an accumulation of Tau in postmortem brains of Alzheimer’s disease patients suggests that the mechanism identified by fruit flies may act similarly in humans. “Human neurons below. Ultimately, we want to prevent this process of abnormal entry of cell division from occurring. It’s an exciting job that we hope to move forward.”