Language
English
Publication Date
2-26-2026
Journal
eLife
DOI
10.7554/eLife.87528
PMID
41744494
PMCID
PMC12945389
PubMedCentral® Posted Date
2-26-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Stress signaling is important for determining the fates of neurons following axonal insults. Previously, we showed that the stress-responsive kinase PERK contributes to injury-induced neurodegeneration (Larhammar et al., 2017). Here, we show that PERK acts primarily through activating transcription factor-4 (ATF4) to stimulate not only pro-apoptotic but also pro-regenerative responses following optic nerve damage. Using conditional knockout mice, we find an extensive PERK/ATF4-dependent transcriptional response that includes canonical ATF4 target genes and modest contributions by C/EBP Homologous Protein (CHOP). Overlap with c-Jun-dependent transcription suggests interplay with a parallel stress pathway that orchestrates regenerative and apoptotic responses. Accordingly, neuronal knockout of ATF4 recapitulates the neuroprotection afforded by PERK deficiency, and PERK or ATF4 knockout impairs optic axon regeneration enabled by disrupting the tumor suppressor PTEN. These findings reveal an integral role for PERK/ATF4 in coordinating neurodegenerative and regenerative responses to CNS axon injury.
Published Open-Access
yes
Recommended Citation
Somasundaram, Preethi; Farley, Madeline M; Rudy, Melissa A; et al., "Coordinated Stimulation of Axon Regenerative and Neurodegenerative Transcriptional Programs by ATF4 Following Optic Nerve Injury" (2026). Faculty, Staff and Students Publications. 7176.
https://digitalcommons.library.tmc.edu/baylor_docs/7176