A novel suppressive effect of alcohol dehydrogenase 5 in neuronal differentiation

Kaiyuan Wu, Ruotong Ren, Wenting Su, Bo Wen, Yuying Zhang, Fei Yi, Xinhua Qiao, Tingting Yuan, Jinhui Wang, Limin Liu, Juan Carlos Izpisua Belmonte*, Guang Hui Liu, Chang Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Alcohol dehydrogenase 5 (ADH5) is a conserved enzyme for alcohol and aldehyde metabolism in mammals. Despite dynamic expression throughout neurogenesis, its role in neuronal development remains unknown. Here we present the first evidence that ADH5 is a negative regulator of neuronal differentiation. Gene expression analyses identify a constant reduction of ADH5 levels throughout neuronal development. Overexpression of ADH5 reduces both development and adult neuronal differentiation of mouse neurons. This effect depends on the catalytic activity of ADH5 and involves ADH5-mediated denitrosation of histone deacetylase 2 (HDAC2). Our results indicate that ADH5 counteracts neuronal differentiation of human neural stem cells and that this effect can be reversed by pharmacological inhibition of ADH5. Based on these observations, we propose that ADH5 is a novel suppressor of neuronal differentiation and maturation. Inhibition of ADH5 may improve adult neurogenesis in a physiological or pathological setting.

Original languageEnglish (US)
Pages (from-to)20193-20199
Number of pages7
JournalJournal of Biological Chemistry
Volume289
Issue number29
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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