期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 294, 期 41, 页码 15095-15103出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA119.008491
关键词
amyotrophic lateral sclerosis (ALS) (Lou Gehrig disease); astrocyte; neuroprotection; ribonuclease; angiogenin (ANG); motor neuron; neurodegeneration; oxidative stress
资金
- National Institutes of Health [R01 CA073808, P50 AG033514, T32 GM007215]
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.
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