Innate immune adaptor TRIF confers neuroprotection in ALSApril 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."
Related Neurons Articles:
One of the big challenges in the Neuroscience field is to understand how connections and communications trigger our behavior.
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.
When many individual neurons collect data, how do they reach a unanimous decision?
Individual neurons can learn not only single responses to a particular signal, but also a series of reactions at precisely timed intervals.
Putting a turbo engine into an old car gives it an entirely new life -- suddenly it can go further, faster.
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.
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.
For decades, scientists have struggled to develop a comprehensive census of cell types in the brain.
In the brain, patterns of neural activity are perfectly balanced.
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:
The Neuron: Cell and Molecular Biology
by Irwin B. Levitan (Author), Leonard K. Kaczmarek (Author)
The Fourth Edition of The Neuron provides a comprehensive first course in the cell and molecular biology of nerve cells. The book begins with properties of the many newly discovered ion channels that have emerged through mapping of the genome. These channels shape the way a single neuron generates varied patterns of electrical activity. Covered next are the molecular mechanisms that convert electrical activity into the secretion of neurotransmitter hormones at synaptic junctions between neurons. The following section examines the biochemical pathways that are linked to the action of... View Details
The Myth of Mirror Neurons: The Real Neuroscience of Communication and Cognition
by Gregory Hickok (Author)
An essential reconsideration of one of the most far-reaching theories in modern neuroscience and psychology.In 1992, a group of neuroscientists from Parma, Italy, reported a new class of brain cells discovered in the motor cortex of the macaque monkey. These cells, later dubbed mirror neurons, responded equally well during the monkey’s own motor actions, such as grabbing an object, and while the monkey watched someone else perform similar motor actions. Researchers speculated that the neurons allowed the monkey to understand others by simulating their actions in its... View Details
The 7 Secrets of Neuron Leadership: What Top Military Commanders, Neuroscientists, and the Ancient Greeks Teach Us about Inspiring Teams
by W. Craig Reed (Author), Gordon R. England (Foreword)
Leadership techniques backed by the world's most effective teams
The 7 Secrets of Neuron Leadership offers a diverse collection of wisdom and practical knowledge to help you build and lead your most effective team yet. Written by a former U.S. Navy diver, this book draws from the author's experiences and beyond to reveal key truths about the nature of teamwork, and expose the core of effective team leadership. You'll go back to ancient Greece to discover the nine personality types and the seven types of love that form the foundation of human interaction, and learn how... View Details
From Neurons to Neighborhoods : The Science of Early Childhood Development
by Committee on Integrating the Science of Early Childhood Development (Author), Youth, and Families Board on Children (Author), National Research Council (Author), Committee on Integrating the Science of Early Childhood Development (Author), Jack P. Shonkoff (Editor), Deborah A. Phillips (Editor)
How we raise young children is one of today's most highly personalized and sharply politicized issues, in part because each of us can claim some level of "expertise." The debate has intensified as discoveries about our development-in the womb and in the first months and years-have reached the popular media.
How can we use our burgeoning knowledge to assure the well-being of all young children, for their own sake as well as for the sake of our nation? Drawing from new findings, this book presents important conclusions about nature-versus-nurture, the impact of being born into a... View Details
The Neuron: Cell and Molecular Biology
by Irwin B. Levitan (Author), Leonard K. Kaczmarek (Author)
The third edition of The Neuron provides a comprehensive first course in the cell and molecular biology of nerve cells. The first part of the book covers the properties of the many ion channels that shape the way a single neuron generates varied patterns of electrical activity, as well as the molecular mechanisms that convert electrical activity into the secretion of neurotransmitter hormones at synaptic junctions between neurons. The second part covers the biochemical pathways that are linked to the action of neurotransmitters and can alter the cellular properties of neurons or... View Details
From Photon to Neuron: Light, Imaging, Vision
by Philip Nelson (Author)
A richly illustrated undergraduate textbook on the physics and biology of light
Students in the physical and life sciences, and in engineering, need to know about the physics and biology of light. Recently, it has become increasingly clear that an understanding of the quantum nature of light is essential, both for the latest imaging technologies and to advance our knowledge of fundamental life processes, such as photosynthesis and human vision. From Photon to Neuron provides undergraduates with an accessible introduction to the physics of light and offers a unified view... View Details
From Neuron to Brain
by John G. Nicholls (Author), A. Robert Martin (Author), David A. Brown (Author), Mathew E. Diamond (Author), David A. Weisblat (Author), Paul A. Fuchs (Author)
From Neuron to Brain, Fifth Edition, provides a readable, up-to-date book for use in undergraduate, graduate, and medical school courses in neuroscience. As in previous editions, the emphasis is on experiments made by electrical recordings, molecular and cellular biological techniques, and behavioral studies on the nervous system, from simple reflexes to cognitive functions. Lines of research are followed from the inception of an idea to new findings being made in laboratories and clinics today.
A major change is that this edition begins with the anatomy and physiology of the... View Details
The NEURON Book
by Nicholas T. Carnevale (Author), Michael L. Hines (Author)
Assuming no previous knowledge of computer programming or numerical methods, The NEURON Book provides practical advice on how to get the most out of the NEURON software program. Although written primarily for neuroscientists, teachers and students, readers with a background in the physical sciences or mathematics and some knowledge about brain cells and circuits, will also find it helpful. Covering details of NEURON's inner workings, and practical considerations specifying anatomical and biophysical properties to be represented in models, this book uses a problem-solving approach that... View Details
From Neuron to Brain: A Cellular and Molecular Approach to the Function of the Nervous System, Fourth Edition
by John G. Nicholls (Author), A. Robert Martin (Author), Bruce G. Wallace (Author), Paul A. Fuchs (Author)
In the 25 years since From Neuron to Brain was first published, the authors' aim has remained constant—to describe how nerve cells go about their business of transmitting signals, how the signals are put together, and how, out of this integration, higher functions emerge. The new Fourth Edition, while maintaining this focus, has been completely reformatted and updated.
The emphasis, as before, is on experiments, and on the way they are carried out. Using a narrative approach, the authors follow a line from the original inception of a new idea to an account of research being done today.... View Details
The Dynamic Neuron
by John Smythies (Author)
A comprehensive review of current research on synaptic plasticity.
The traditional model of synapses as fixed structures has been replaced by a dynamic one in which synapses are constantly being deleted and replaced. This book, written by a leading researcher on the neurochemistry of schizophrenia, integrates material from neuroscience and cell biology to provide a comprehensive account of our current knowledge of the neurochemical basis of synaptic plasticity.
The book presents the evidence for synaptic plasticity, an account of the dendritic spine and the glutamate... View Details