Nav: Home

Innate immune adaptor TRIF confers neuroprotection in ALS

April 15, 2018

Nagoya, Japan - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease damaging motor neurons in brain and spinal cords. ALS patients show progressive muscle weakness and atrophy, leading to a fatal respiratory muscle paralysis. There are no effective therapies for ALS.

There are compelling evidence that glial and immune cells contribute to the progression of neurodegenerative diseases including ALS. The adaptive immune response has been implicated in disease processes of ALS, but it remains unknown if innate immune signaling also contributes to ALS progression.

Now, the research group led by Professor Koji Yamanaka at Nagoya University revealed that deficiency of the innate immune adaptor TRIF, which is essential for certain Toll-like receptor (TLR) signaling cascades, significantly shortened survival time of ALS mice.

To test the role of innate immune response in the mouse model of ALS, the researchers focused on Toll-like receptors (TLR), which are important sensors for innate immunity. TLR signaling requires TRIF and MyD88, two critical adaptor proteins for transmitting signals. "We found that ablation of TRIF significantly shortens survival time of ALS mice," says Okiru Komine, first author of the study. "While MyD88 is also a crucial adaptor for most TLR signaling pathways, MyD88 deficiency had no impact on disease course."

In addition, they found that aberrantly activated astrocytes were accumulated in the lesions of TRIF-deficient ALS mice. Astrocytes, one type of glial cells are the supporting cells for survival and function of neurons in the brain by secreting many kinds of neuroprotective molecules. However, in the lesion of ALS, astrocytes change their shapes and some of them are abnormally activated to secrete the harmful molecules to the neurons.

These aberrantly activated astrocytes overproduced toxic reactive oxygens. Researchers found TRIF signaling is able to eliminate these aberrantly activated astrocytes by apoptosis, a suicide program of the cells. In the absence of TRIF, these astrocytes were accumulated. Moreover, the number of aberrantly activated astrocytes was negatively correlated with survival time of ALS mice, suggesting that these astrocytes are toxic to the motor neurons.

"These results revealed for the first time that the TRIF pathway is involved in eliminating aberrantly activated astrocytes to maintain the microenvironment surrounding motor neurons in ALS mice," Yamanaka says. "The current study reveals the new roles of innate immunity in ALS pathomechanism and provides a clue to develop a new therapeutic approach for protecting ALS motor neurons."
-end-
The article, "Innate immune adaptor TRIF deficiency accelerates disease progression of ALS mice with accumulation of aberrantly activated astrocytes", was published in Cell Death & Differentiation, at DOI:10.1038/s41418-018-0098-3.

Nagoya University

Related Neurons Articles:

How do we get so many different types of neurons in our brain?
SMU (Southern Methodist University) researchers have discovered another layer of complexity in gene expression, which could help explain how we're able to have so many billions of neurons in our brain.
These neurons affect how much you do, or don't, want to eat
University of Arizona researchers have identified a network of neurons that coordinate with other brain regions to influence eating behaviors.
Mood neurons mature during adolescence
Researchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood.
Astrocytes protect neurons from toxic buildup
Neurons off-load toxic by-products to astrocytes, which process and recycle them.
Connecting neurons in the brain
Leuven researchers uncover new mechanisms of brain development that determine when, where and how strongly distinct brain cells interconnect.
The salt-craving neurons
Pass the potato chips, please! New research discovers neural circuits that regulate craving and satiation for salty tastes.
When neurons are out of shape, antidepressants may not work
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD.
Losing neurons can sometimes not be that bad
Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease.
Neurons that fire together, don't always wire together
As the adage goes 'neurons that fire together, wire together,' but a new paper published today in Neuron demonstrates that, in addition to response similarity, projection target also constrains local connectivity.
Scientists accidentally reprogram mature mouse GABA neurons into dopaminergic-like neurons
Attempting to make dopamine-producing neurons out of glial cells in mouse brains, a group of researchers instead converted mature inhibitory neurons into dopaminergic cells.
More Neurons News and Neurons Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.