A new signalling pathway has been discovered that could shed light on damage repair during brain injury.
The new understanding of what causes neural cells to enter divisions after damage in the brain is a “valuable opportunity” to potentially prevent neuronal death or neurodegeneration following injury.
The research, led by the University of Plymouth, explores how most human cells are able to repair damage by dividing at wounds – but mature nerve cells, or neurons, will most probably die if they attempt division. This happens during brain injury or in conditions including Alzheimer’s Disease.
But now, the study has uncovered a pathway that has shed new light on how these divisions may be triggered. The research focuses on intracellular structures called microtubules – which are found in most animal cells, and can be damaged by a build-up of a protein called Tau in the brain during Alzheimer’s.
The study was conducted in fruit flies, with comparison to postmortem brain samples of Alzheimer’s patients, with findings showing that when the microtubules of neural cells in fruit flies are damaged, division is triggered via activating the small signalling kinases, Tak1 and Ik2.
Activation of these molecules can also be seen in brains of people with Alzheimer’s.
“While other scientists are exploring Tau and how it builds up, we’re looking more at what happens to the cell after it has been damaged,” says Dr Torsten Bossing, of Plymouth Institute of Health and Care Research (PIHR), who led the research.
“The fact that the identified two signalling kinases are found alongside a build-up of Tau in post mortem brains of Alzheimer’s Disease patients suggests that the mechanism identified using fruit flies may act similarly in humans. So we want to further our studies by using cultured human neurons next.
“Ultimately we want to prevent this abnormal cell division entry process from happening in the first place. It’s an exciting piece of work, which we look forward to progressing.”
The team say that by understanding how the damaged microtubules behave, the potential exists to prevent neuronal death following brain injury, or upon neurodegeneration, such as in Alzheimer’s.
While the research took place in fruit flies, the team tested the applicability of their results by making fly neural cells express human Tau, and also examining post mortem human brain samples from Alzheimer’s patients.
Abnormal human Tau destroys microtubules in both flies’ and Alzheimer’s brains, and interestingly can trigger the same signalling cascade as discovered in fly neural cells after microtubule damage.
The researchers also found that higher levels of Tau accumulation correlated to a greater frequency of neurons attempting to divide and neuronal death, but have not yet established a direct link or cause.
