Angiogenin activates the astrocytic Nrf2/antioxidant-response element pathway and thereby protects murine neurons from oxidative stress
Author(s)Hoang, Trish T.; Johnson, Delinda A.; Raines, Ronald T; Johnson, Jeffrey A.
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The angiogenin (ANG) gene is mutated frequently in individuals with amyotrophic lateral sclerosis (ALS), a fatal neurode-generative 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 inhibitionoftranslation 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 occurredinastrocytes but notin 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.
DepartmentMassachusetts Institute of Technology. Department of Chemistry
Journal of Biological Chemistry
American Society for Biochemistry & Molecular Biology (ASBMB)
Hoang, Trish T. et al. "Angiogenin activates the astrocytic Nrf2/antioxidant-response element pathway and thereby protects murine neurons from oxidative stress." Journal of Biological Chemistry 294, 41 (August 2019): 15095-15103 © 2019 The Authors
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