♦ See referenced article, J. Biol. Chem. 2012, 287, 35444–35453
Previous reports had showed that a histone deacetylase called HDAC1 had contradictory effects on neurons. It appeared to both protect and poison neurons. In this Paper of the Week, a team led by Santosh R. D'Mello at the University of Texas at Dallas described how HDAC1 could carry out two seemingly conflicting roles. By using two mouse models for neurodegeneration, the investigators showed that HDAC1 paired with another histone deacetylase called HDAC3 caused neuronal death. However, if HDAC1 partnered with a different histone deacetylase called histone deacetylase-related protein (HDRP), the pair protected the neuron from cell death. The authors say, “Together, our results suggest that HDAC1 is a molecular switch between neuronal survival and death.”
The viability of neurons transfected with GFP, HDAC1, or HDAC3 or co-transfected with HDAC1 and HDAC3 was assessed. The right panel shows knockdown of HDAC1 by one of two short hairpin RNAs.