Angiogenin activates the astrocytic Nrf2/antioxidant-response element pathway and thereby protects murine neurons from oxidative stress

J Biol Chem. 2019 Oct 11;294(41):15095-15103. doi: 10.1074/jbc.RA119.008491. Epub 2019 Aug 20.


The angiogenin (ANG) gene is mutated frequently in individuals with amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Delivering human ANG to mice that display ALS-like symptoms extends their lifespan and improves motor function. ANG is a secretory vertebrate RNase that enters neuronal cells and cleaves a subset of tRNAs, leading to the inhibition of translation initiation and the assembly of stress granules. Here, using murine neuronal and astrocytic cell lines, we find that ANG triggers the activation of the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway, which provides a critical cellular defense against oxidative stress. This activation, which occurred in astrocytes but not in neurons, promoted the survival of proximal neurons that had oxidative injury. These findings extend the role of ANG as a neuroprotective agent and underscore its potential utility in ALS management.

Keywords: amyotrophic lateral sclerosis (ALS) (Lou Gehrig disease); angiogenin (ANG); astrocyte; motor neuron; neurodegeneration; neuroprotection; nuclear factor 2 (erythroid-derived 2-like factor) (NFE2L2) (Nrf2); oxidative stress; ribonuclease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antioxidant Response Elements / drug effects*
  • Astrocytes / cytology
  • Astrocytes / drug effects*
  • Astrocytes / metabolism*
  • Cell Line
  • Mice
  • NF-E2-Related Factor 2 / metabolism*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects*
  • Ribonuclease, Pancreatic / pharmacology*
  • Signal Transduction / drug effects


  • NF-E2-Related Factor 2
  • Neuroprotective Agents
  • angiogenin
  • Ribonuclease, Pancreatic