The manuscript identifies a novel role of angiogenin, a member of the pancreatic RNase A superfamily, in communication between neurons and glia in the spinal cord. Mutations in angiogenin are associated with amyotrophic lateral sclerosis; therefore, its functions in the spinal cord are of great importance. Authors propose that angiogenin is secreted from motor neurons upon stress and internalized by astrocyte cultures, such that its RNase activity has a paracrine effect on astroglia. Whereas the authors demonstrate increased RNA cleavage upon serum withdrawal in astroglia, the identity of the cleaved RNAs and the direct role of angiogenin in the cleavage are still unclear. However, the authors provide substantial evidence for a role of clathrin-dependent vesicle transport and syndecan-4 receptor in angiogenin internalization by astrocytes. Importantly, such paracrine function of angiogenin creates new opportunities for neuroprotective therapies.

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