Brain-derived neurotrophic factor suppresses tunicamycin-induced upregulation of CHOP in neurons

Gang Chen, Zhiqin Fan, Xin Wang, Cuiling Ma, Kimberly A. Bower, Xianglin Shi, Zun Ji Ke, Jia Luo

Research output: Contribution to journalArticlepeer-review

44 Citations (SciVal)


The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen triggers ER stress. ER stress initiates a number of specific compensatory signaling pathways including unfolded protein response (UPR). UPR is characterized by translational attenuation, synthesis of ER chaperone proteins such as glucose-regulated protein of 78 kDa (GRP78, also known as Bip), and transcriptional induction, which includes the activation of transcription factors such as activating transcriptional factor 6 (ATF6) and C/EBP homologous protein (CHOP, also known as growth arrest and DNA damage-inducible gene 153 [GADD153]). Sustained ER stress ultimately leads to cell death. ER functions are believed to be impaired in various neurodegenerative diseases, as well as in some acute disorders of the brain. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, functions as a neuroprotective agent and rescues neurons from various insults. The molecular mechanisms underlying BDNF neuroprotection, however, remain to be elucidated. We showed that CHOP partially mediated ER stress-induced neuronal death. BDNF suppressed ER stress-induced upregulation/nuclear translocation of CHOP. The transcription of CHOP is regulated by ATF4, ATF6, and XBP1; BDNF selectively blocked the ATF6/CHOP pathway. Furthermore, BDNF inhibited the induction of death receptor 5 (DR5), a transcriptional target of CHOP. Our study thus suggests that suppression of CHOP activation may contribute to BDNF-mediated neuroprotection during ER stress responses.

Original languageEnglish
Pages (from-to)1674-1684
Number of pages11
JournalJournal of Neuroscience Research
Issue number8
StatePublished - Jun 2007


  • Cell death
  • Endoplasmic reticulum stress
  • Neurodegeneration
  • Neuroprotection
  • Neurotrophic factor

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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