The star-shaped cells usually help clear away toxic particles that build up in the brain naturally or after head trauma, and are supposed to nourish neurons. But laboratory tests on mice show astrocytes also release toxic fatty acids to kill off damaged neurons, confirming a suspicion many neurologists have had for years. “Our findings show the toxic fatty acids produced by astrocytes play a critical role in brain cell death. The results provide a promising new target for treating, and perhaps even preventing, many neurodegenerative diseases”.

Astrocytes regulate the response of the central nervous system to disease and injury and have been hypothesized to actively kill neurons in neurodegenerative disease. Here we report an approach to isolate one component of the long-sought astrocyte-derived toxic factor. Notably, instead of a protein, saturated lipids contained in APOE and APOJ lipoparticles mediate astrocyte-induced toxicity. Eliminating the formation of long-chain saturated lipids by astrocyte-specific knockout of the saturated lipid synthesis enzyme ELOVL1 mitigates astrocyte-mediated toxicity in vitro as well as in a model of acute axonal injury in vivo. These results suggest a mechanism by which astrocytes kill cells in the central nervous system.

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