Microglia caught eating living motor neurons in ALS mice via unexpected immune pathway
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that, according to the CDC, currently affects around 35,000 Americans—with 5,000 more diagnosed each year. Risk climbs with age, and treatments only slow progression. With no cure and an aging population, scientists are urgently seeking insights that could change those devastating outcomes.
Microglia, immune cells found in the brain and spinal cord, have been observed by researchers at the Salk Institute to be actively consuming living motor neurons in mice with amyotrophic lateral sclerosis (ALS). This novel immune pathway was discovered through the investigation of a well-known mouse model of ALS, called SOD1, which expresses a mutant protein causing ALS in humans.
The Salk researchers found that the motor neurons of these mice were being systematically eaten by microglia, and that the levels of TAM proteins—proteins crucial for cell destruction—were elevated in these mice. Microglia use TAM receptors, a class of proteins that facilitate cell destruction, to locate and kill motor neurons in the spinal cords of ALS mice.
When the Salk team disabled two TAM family proteins, Axl and Mer, the mice progressed faster but lived longer, indicating that the TAM system was somehow preventing the microglia from consuming the neurons. This discovery, published in Nature Communications, is the first time the TAM system has been shown to target living cells.
While the study does not suggest that removing the TAM system as a therapy would be effective, it does provide fundamental insights into microglia biology, neuronal biology, and immunology that could be beneficial in the research of other neurodegenerative diseases such as Alzheimer's and Parkinson's.
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