Nav: Home

Enzyme helps build motor that drives neuron death

August 06, 2018

A biochemistry instructor curious about an enzyme discovered in the damaged neurons of people with multiple sclerosis made a leap toward a potential cure for countless neurodegenerative ills.

Vanderbilt University's Amrita Pathak, working with Bruce D. Carter, biochemistry professor and associate director of the Vanderbilt Brain Institute, found that the enzyme histone deacetylase 1 (HDAC1), normally in the nucleus of cells, is also present in the axons of some neurons. When a degenerative signal is activated, HDAC1 modifies a component of a molecular motor, which then drives a signaling agent down the axon to the neuron's cell body, killing it.

The motor is integral to that process, Carter said, because of the extreme length of axons in some neurons.

"Some of our neurons, if their cell bodies were the size of basketballs, their axons would reach about 6 miles," he said. "This is a new finding in terms of how the motor can be assembled and allow transport back to the cell body. There has been evidence of a retrograde degenerative signal, and now we've identified key components and a mechanism controlling their transport."

Their paper, "Retrograde degenerative signaling mediated by the p75 neurotrophin receptor requires p150glued deacetylation by axonal HDAC1," appears online today in the journal Developmental Cell.

The biochemistry team worked with Deyu Li, professor of mechanical engineering, to build microfluidic devices that separate the axon from the cell body, allowing them to determine which part of the degenerative signaling process was happening where.

The Carter laboratory has long studied that signaling agent, the neurotrophin receptor p75(NTR), and the role it plays in development and diseases of the brain. It's implicated in Alzheimer's disease, amyotrophic lateral sclerosis, traumatic brain injury, ischemia, hormone deficiency and other diseases or injuries to the nervous system.

Their research builds on the work of Vanderbilt University biochemist Stanley Cohen, who in 1986 shared the Nobel Prize for Physiology or Medicine for the discovery of nerve growth factor, the founding member of the neurotrophin family, and its effect on cells, Carter said.

Pathak, who used sympathetic neurons for her research, intends to find whether similar cellular processes are happening in motor neurons known to be affected in ALS. "If we can block that, we can block the neuron death that occurs," she said.
-end-


Vanderbilt University

Related Neurons Articles:

New tool to identify and control neurons
One of the big challenges in the Neuroscience field is to understand how connections and communications trigger our behavior.
Neurons that regenerate, neurons that die
In a new study published in Neuron, investigators report on a transcription factor that they have found that can help certain neurons regenerate, while simultaneously killing others.
How neurons use crowdsourcing to make decisions
When many individual neurons collect data, how do they reach a unanimous decision?
Neurons can learn temporal patterns
Individual neurons can learn not only single responses to a particular signal, but also a series of reactions at precisely timed intervals.
A turbo engine for tracing neurons
Putting a turbo engine into an old car gives it an entirely new life -- suddenly it can go further, faster.
Brain neurons help keep track of time
Turning the theory of how the human brain perceives time on its head, a novel analysis in mice reveals that dopamine neuron activity plays a key role in judgment of time, slowing down the internal clock.
During infancy, neurons are still finding their places
Researchers have identified a large population of previously unrecognized young neurons that migrate in the human brain during the first few months of life, contributing to the expansion of the frontal lobe, a region important for social behavior and executive function.
How many types of neurons are there in the brain?
For decades, scientists have struggled to develop a comprehensive census of cell types in the brain.
Molecular body guards for neurons
In the brain, patterns of neural activity are perfectly balanced.
Engineering researchers use laser to 'weld' neurons
University of Alberta researchers have developed a method of connecting neurons, using ultrashort laser pulses -- a breakthrough technique that opens the door to new medical research and treatment opportunities.

Related Neurons Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Setbacks
Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".