Scientists identify how normally protective immune responses kill neurons

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.