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. Scientists are examining how SARM1 interacts with mitochondria in the axons to induce death of the nerve cells. Credit: NIAID
Many brain disorders involve the death of neurons, or nerve cells, but how these neurons die is not well understood. A new study 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.
Researchers from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) studied the effect of immune system proteins: toll-like receptors on neurons. These receptors detect infection by bacteria or viruses and 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.
MOA: Toll-like receptors activated a protein called SARM1 in neurons, which induces their death by affecting the function of mitochondria.
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.
http://www.niaid.nih.gov/news/newsreleases/2015/Pages/SARM1.aspx
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