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Study Reveals Why Protective Immune Response Can Sometimes Kill Neurons
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Study Reveals Why Protective Immune Response Can Sometimes Kill Neurons

FeaturedNeurology
·October 6, 2015

National Institutes of Health (NIH) scientists studying inflammation of the brain have discovered why certain immune responses, which typically help cells recognize and fight viral and bacterial infections, can sometimes be harmful to the brain. Many brain disorders involve the death of neurons, or nerve cells, but how these neurons die is not well understood. A new study in The Journal of Immunology describes how the activation of normally protective immune responses causes nerve cells to die and identifies the protein responsible, providing a potential target for therapeutic intervention.

Image shows SARM1 in neurons.
The immune system protein SARM1 (red) extends to the string-like fibers (axons) of nerve cells in the brains of mice infected with La Crosse virus. Credit: NIAID.

Researchers from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) studied the effect of immune system proteins called toll-like receptors on neurons. These receptors detect infection by bacteria or viruses. They also can detect certain molecules released by dying neurons and associated with diseases such as Alzheimer’s. The researchers used a mouse model to study why stimulation of these receptors caused death in neurons, but not other cell types. They determined that toll-like receptors activated a protein called SARM1 in neurons, which induces their death by affecting the function of mitochondria, the cells’ energy producers.

The study builds on the NIAID group’s previous work showing that SARM1 also caused neuronal death during viral infections in the brain. The new research demonstrates that immune activation of neurons, even in the absence of viral infection, can cause them to die. By identifying SARM1 as a key molecule responsible for this process, researchers have an improved understanding of why the normally protective immune response can be detrimental when infection or damage occurs in the brain.

About this neurology research

Funding: This research was supported by NIH/National Institute of Allergy and Infectious Diseases.

Source: Ken Pekoc – NIH/NIAID
Image Source: The image is in the public domain
Original Research: Abstract for “SARM1, Not MyD88, Mediates TLR7/TLR9-Induced Apoptosis in Neurons” by Piyali Mukherjee, Clayton W. Winkler, Katherine G. Taylor, Tyson A. Woods, Vinod Nair, Burhan A. Khan and Karin E. Peterson in Journal of Immunology. Published online September 30 2015 doi:10.4049/​jimmunol.1500953


Abstract

See also
This shows the white matter tract in the brain's reading network
FeaturedNeuroscience
·February 24, 2022·5 min read

Assessing Connections in the Brain’s Reading Network

SARM1, Not MyD88, Mediates TLR7/TLR9-Induced Apoptosis in Neurons

Neuronal apoptosis is a key aspect of many different neurologic diseases, but the mechanisms remain unresolved. Recent studies have suggested a mechanism of innate immune-induced neuronal apoptosis through the stimulation of endosomal TLRs in neurons. TLRs are stimulated both by pathogen-associated molecular patterns as well as by damage-associated molecular patterns, including microRNAs released by damaged neurons. In the present study, we identified the mechanism responsible for TLR7/TLR9-mediated neuronal apoptosis. TLR-induced apoptosis required endosomal localization of TLRs but was independent of MyD88 signaling. Instead, apoptosis required the TLR adaptor molecule SARM1, which localized to the mitochondria following TLR activation and was associated with mitochondrial accumulation in neurites. Deficiency in SARM1 inhibited both mitochondrial accumulation in neurites and TLR-induced apoptosis. These studies identify a non–MyD88 pathway of TLR7/ TLR9 signaling in neurons and provide a mechanism for how innate immune responses in the CNS directly induce neuronal damage.

“SARM1, Not MyD88, Mediates TLR7/TLR9-Induced Apoptosis in Neurons” by Piyali Mukherjee, Clayton W. Winkler, Katherine G. Taylor, Tyson A. Woods, Vinod Nair, Burhan A. Khan and Karin E. Peterson in Journal of Immunology. Published online September 30 2015 doi:10.4049/​jimmunol.1500953

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Neuroscience News
Neuroscience News posts science research news from labs, universities, hospitals and news departments around the world. Science articles can cover neuroscience, psychology, AI, robotics, neurology, brain cancer, mental health, machine learning, autism, Parkinson's, Alzheimer's, brain research, depression and other topics related to cognitive sciences.
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This shows the outline of a woman and a brain

How the Brain Changes During Depression Treatment

This shows a man sitting with a bottle at the side of a road

Deaths From Alcohol Use Disorder Surged During Pandemic

This shows brain scans from the study

How the Volumes of Brain Regions Change in Parkinson’s Disease

This shows a woman looking out of a window covered in rain

Medication Treatment of Pediatric Psychiatric Disorders Reduces the Later Onset of Substance Use Problems

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