Researchers discover how neurons tell each other to die under trauma, disease

March 9, 2017, University of Virginia

A major contributor to most neurological diseases is the degeneration of a wire-like part of nerve cells called an axon, which electrically transmits information from one neuron to another. The molecular programs underlying axon degeneration are therefore important targets for therapeutic intervention - the idea being that if axons can be preserved, rather than allowed to die in diseased conditions, then loss of critical processes like movement, speech or memory will be slowed.

For more than 150 years, researchers believed that axons died independently of one another when injured as a result of trauma, such as stroke or , or of a neurological disease, such as Alzheimer's.

But a new study by University of Virginia researchers challenges this idea and suggests that axons coordinate each other's destruction, thereby contributing to the degeneration that makes so devastating and permanent.

The paper appears in the March 20 issue of the journal Current Biology.

"We are the first to demonstrate that a receptor known to convey information from the outside of the cell to the inside of the cell is essential for axon degeneration after injury," said study co-author Christopher Deppmann, a UVA biology, neuroscience, cell biology and biomedical engineering professor. "This implies that axons talk to each other while they are dying, and an injured axon can coax an uninjured neighbor to die, too."

This creates a ripple effect of neuron death that confounds efforts to restore the growth of healthy cells. However, the researchers also found that the death spiral can be slowed when this communication is blocked using a laboratory method that could inspire pharmacological therapies to treat pathological . The method demonstrates that injured axons can be preserved for at least 10 times longer when their communication with neighbors is blocked.

"This represents a paradigm shift for how we think about the ways the nervous system is torn apart during pathology," Deppmann said. "It opens a possible new avenue for the development of therapies that may be promising for slowing or stopping the effects of Alzheimer's disease, and spinal cord injury."

Deppmann and his graduate student, Kanchana Gamage, the study's lead author, believe that axons communicate the death message to each other during injury as a leftover activity, "borrowed" from the nervous system's developmental period when axons are overproduced and then improper or unnecessary connections are eliminated by a similar communication between axons. While this process is essential during development, it appears to be hijacked in diseased or traumatic conditions to reactivate and accelerate neuron degeneration.

The researchers have found that axons receive the message to die as a chemical signal via a known as "death receptor 6." They speculate that this chemical signal is released from the axon itself, and they currently are working to determine the identity of this .

"Knowing this, it may be possible that for diseases such as Alzheimer's and Parkinson's, a drug could be developed to block the axon receptors from receiving the specific message that leads to degeneration," Gamage said. "If so, the damage to healthy cells could be slowed or stopped. Essentially, we could tell not to pick up the phone if a degeneration signal is on the other line."

Explore further: Molecule shown to repair damaged axons

More information: Current Biology. DOI: 10.1016/j.cub.2017.01.062

Related Stories

Molecule shown to repair damaged axons

March 8, 2017
A foray into plant biology led one researcher to discover that a natural molecule can repair axons, the thread-like projections that carry electrical signals between cells. Axonal damage is the major culprit underlying disability ...

Major pathway identified in nerve cell death offers hope for therapies

April 23, 2015
New research highlights how nerves - whether harmed by disease or traumatic injury - start to die, a discovery that unveils novel targets for developing drugs to slow or halt peripheral neuropathies and devastating neurodegenerative ...

New clues to halting nerve degeneration

December 10, 2015
A discovery into the mechanisms which lead to degeneration and loss of communication among neuron cells - the cells controlling function in the brain and nervous system - could potentially lead to future therapies for neurodegenerative ...

Scientists question a popular theory about how the nervous system trims its branches

February 18, 2016
As tiny embryos in the womb, we start out with a lot more neuronal material than we actually need. During development, the body drastically prunes back the excess—cutting the branches from nerve cell bodies, known as axons, ...

Spinal cord axon injury location determines neuron's regenerative fate

April 30, 2015
Researchers at University of California, San Diego School of Medicine report a previously unappreciated phenomenon in which the location of injury to a neuron's communication wire in the spinal cord—the axon—determines ...

Tiny worm opens big discovery on nerve degeneration

February 11, 2016
A discovery in a transparent roundworm has brought scientists one step closer to understanding nerve degeneration.

Recommended for you

Brain activity linked to stress changes chemical codes

April 24, 2018
Five years ago, a team of University of California San Diego neurobiologists published surprising findings describing how rats' brain cells adopted new chemical codes when subjected to significant changes in natural light ...

In Huntington's disease, heart problems reflect broader effects of abnormal protein

April 24, 2018
Researchers investigating a key signaling protein in Huntington's disease describe deleterious effects on heart function, going beyond the disease's devastating neurological impact. By adjusting protein levels affecting an ...

Heading—not collisions—cognitively impairs players

April 24, 2018
Worse cognitive function in soccer players stems mainly from frequent ball heading rather than unintentional head impacts due to collisions, researchers at Albert Einstein College of Medicine have found. The findings suggest ...

Imagined and actual movements are controlled by the brain in the same way

April 24, 2018
A new study from Karolinska Institutet in Sweden shows that imagined movements can change our perception in the same way as real, executed movements do. The research, which is presented in the scientific journal Nature Communications, ...

Scientists develop new method that uses light to manage neuropathic pain in mice

April 24, 2018
For patients with neuropathic pain, a chronic condition affecting 7 to 8 percent of the European population, extreme pain and sensitivity are a daily reality. There is currently no effective treatment. Scientists from EMBL ...

Animal cyborg—behavioral control by activating 'toy craving' circuit

April 24, 2018
Children love to get toys from parents as presents. This craving for objects also underlies object hoarding disorders and shopping addiction. However, the biological causes of object pursuit have remained unknown. Part of ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.