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J Biol Chem. 2019 Aug 20. pii: jbc.RA119.008491. doi: 10.1074/jbc.RA119.008491. [Epub ahead of print]

Angiogenin activates the astrocytic Nrf2/ARE pathway and thereby protects murine neurons from oxidative stress.

Author information

1
University of Wisconsin-Madison, United States.
2
Department of Chemistry, Massachusetts Institute of Technology, United States.

Abstract

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 ribonuclease 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 nuclear factor erythroid 2-related factor 2 (Nrf2) 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:

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

PMID:
31431502
DOI:
10.1074/jbc.RA119.008491
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