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HDAC6 Modulates Signaling Pathways Relevant to Synaptic Biology and Neuronal Differentiation in Human Stem Cell-Derived Neurons

by 1,2, 1,2 and 1,2,3,4,5,*
1
Center for Genomic Medicine, Harvard Medical School and Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA
2
Chemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
3
Schizophrenia and Bipolar Disorder Program, McLean Hospital, Belmont, MA 02478, USA
4
Program in Neuroscience, Harvard University, Cambridge, MA 02138, USA
5
Chemical Biology PhD Program, Harvard University, Cambridge, MA 02138, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1605; https://doi.org/10.3390/ijms20071605
Received: 21 January 2019 / Revised: 12 March 2019 / Accepted: 18 March 2019 / Published: 31 March 2019
(This article belongs to the Special Issue Histone Deacetylase Inhibitors in Health and Disease)
Recent studies show that histone deacetylase 6 (HDAC6) has important roles in the human brain, especially in the context of a number of nervous system disorders. Animal models of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders show that HDAC6 modulates important biological processes relevant to disease biology. Pan-selective histone deacetylase (HDAC) inhibitors had been studied in animal behavioral assays and shown to induce synaptogenesis in rodent neuronal cultures. While most studies of HDACs in the nervous system have focused on class I HDACs located in the nucleus (e.g., HDACs 1,2,3), recent findings in rodent models suggest that the cytoplasmic class IIb HDAC, HDAC6, plays an important role in regulating mood-related behaviors. Human studies suggest a significant role for synaptic dysfunction in the prefrontal cortex (PFC) and hippocampus in depression. Studies of HDAC inhibitors (HDACi) in human neuronal cells show that HDAC6 inhibitors (HDAC6i) increase the acetylation of specific lysine residues in proteins involved in synaptogenesis. This has led to the hypothesis that HDAC6i may modulate synaptic biology not through effects on the acetylation of histones, but by regulating acetylation of non-histone proteins. View Full-Text
Keywords: HDAC6; HDAC inhibitor; acetylation; β-catenin; AKT; synapse; neuronal differentiation HDAC6; HDAC inhibitor; acetylation; β-catenin; AKT; synapse; neuronal differentiation
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MDPI and ACS Style

Iaconelli, J.; Xuan, L.; Karmacharya, R. HDAC6 Modulates Signaling Pathways Relevant to Synaptic Biology and Neuronal Differentiation in Human Stem Cell-Derived Neurons. Int. J. Mol. Sci. 2019, 20, 1605. https://doi.org/10.3390/ijms20071605

AMA Style

Iaconelli J, Xuan L, Karmacharya R. HDAC6 Modulates Signaling Pathways Relevant to Synaptic Biology and Neuronal Differentiation in Human Stem Cell-Derived Neurons. International Journal of Molecular Sciences. 2019; 20(7):1605. https://doi.org/10.3390/ijms20071605

Chicago/Turabian Style

Iaconelli, Jonathan; Xuan, Lucius; Karmacharya, Rakesh. 2019. "HDAC6 Modulates Signaling Pathways Relevant to Synaptic Biology and Neuronal Differentiation in Human Stem Cell-Derived Neurons" Int. J. Mol. Sci. 20, no. 7: 1605. https://doi.org/10.3390/ijms20071605

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