A novel suppressive effect of alcohol dehydrogenase 5 in neuronal differentiation.


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.

DOI: 10.1074/jbc.C114.561860

Cite this paper

@article{Wu2014ANS, title={A novel suppressive effect of alcohol dehydrogenase 5 in neuronal differentiation.}, author={Kaiyuan Wu and Ruotong Ren and Wenting Su and Bo Wen and Yuying Zhang and Fei Yi and Xinhua Qiao and Tingting Yuan and Jinhui Wang and Limin Liu and Juan Carlos Izpisua Belmonte and Guang-Hui Liu and Chang Chen}, journal={The Journal of biological chemistry}, year={2014}, volume={289 29}, pages={20193-9} }