Taking a Toll on neurons

Battling pathogens and shaping neuronal growth seem to have as much in common as accounting and skydiving. But both tasks involve one of the Toll-like proteins, as Ma et al. report on page 209. The study is the first to discover a function for a member of the Toll-like family within neurons.

Toll-like receptors (TLRs) enable mammalian immune cells to identify interlopers. TLR8, for instance, recognizes RNA on the loose, a sign of viral infection or cell destruction. The Drosophila equivalents of the proteins, the Toll receptors, also supervise synapse formation and axon growth, researchers have discovered. Although previous studies had revealed that mammalian neurons manufacture TLRs, no one had shown that the molecules performed a job in these cells.

Ma et al. found that brain levels of TLR8 shot up in the early mouse embryo and fell after birth, suggesting that the molecule participates in nervous system development. To clarify its role, the researchers dosed embryonic brain cells with a compound that stimulates TLR8. The treatment impeded the growth of neurites, the branches that sprout from developing neurons, and spurred some of the cells to kill themselves. An antibody that latches onto TLR8 prevented both effects.

TLR8 usually raises the alarm by activating the signaling pathway headed by NF-κB. But Ma et al. showed that NF-κB remained off in neurons, indicating that the receptor acts in these cells through an unidentified pathway. The researchers speculate that TLR8 might serve as a danger detector in neurons. If it senses infection or tissue damage, it may deter neurons from entering the trouble spot by pruning their neurites or triggering their suicide.