Metabolic signals in neurons determine if axons degrade or resist neurodegeneration, the study reveals

Unlike most cells in the human body, neurons – functional cells in our nervous system – can generally be replaced by healthy copies after being damaged.

On the contrary, after an injury of something like a stroke, a concussion or a neurodegenerative disease, neurons and their axons, fiber type projections which relay electrical signals, are much more likely to degrade than to regenerate.

But new research from the University of Michigan is opening up new ways of thinking about neurodegeneration that could help protect patients against this degradation and this neurological decline in the future.

The study, published in the journal Molecular metabolismCould even bring us closer to understanding the rare cases when the brains heal and open new paths to the development of treatments, the researchers said.

Their results, manufactured using a well -established fruit fly model, suggest that the resilience of neurons to degradation is linked to the fundamental process of the way these cells treat sugar. The work was supported by the National Institutes of Health, the US National Science Foundation, the Rita Allen Foundation and the Klingenstein Fellowship in the Neuroscience.

“Metabolism is often modified in brain damage and diseases such as Alzheimer’s disease, but we do not know if it is a cause or consequence of the disease,” said the main monica DUS, UM associate professor of molecular, cellular and developmental biology.

“Here, we have found that the numbering of sugar metabolism decomposes neuronal integrity, but if neurons are already injured, the same manipulation can activate a protection program preventively. Instead of decomposing, axons are held longer.”

The postdoctoral researcher TJ Waller, the main scientist of the study, revealed that two particular proteins seem to be involved in the extension of the health of axons. One is called a double zipper of Leucine Kinase, or DLK, which detects neural damage, and is activated by a disturbed metabolism.

The other protein is known as Sarm1 – Short for alpha sterile and containing shooting motif 1 – which was involved in the degeneration of axons and is coupled with the DLK response.

“What surprised us is that the neuroprotective response changes according to the internal conditions of the cell,” said DUS. “Metabolic signals are shaped, that neurons hold the line or begin to decompose.”

Generally, in cases where neurons and axons do not deteriorate, the DLK becomes more active and the movement of SARM1 is deleted. But there are wrinkles. In fact, prolonged activation of the DLK over time leads to a progressive neurodegeneration, has shown that the study has shown, effectively reversing the previous neuroprotective effects.

The DLK, in particular, has become a target to treat and study neurodegenerative disease. But researchers will have to face technical challenges to control the double harmful and beneficial DLK features, Waller said.

“If we want to delay the progress of a disease, we want to inhibit its negative appearance,” said Waller. “We want to make sure that we do not inhibit the more positive aspect that could really help slow the disease naturally.”

Mediation of a molecule like DLK’s double functionality presents a puzzle convincing that researchers have not yet resolved. The discovery of mechanisms underlying the way modulators like DLK switch between these protective and harmful states could have massive implications for the treatment of neurodegenerative diseases and brain damage, directly impacting clinical populations.

DUS and Waller said that understanding this mechanism “provides a new perspective on injuries and diseases, which goes beyond the simple blocking of damage to focus on what the system is already doing to strengthen it.”