The vastly more superior regenerative capacity of the axons of peripheral nerves over central nervous system (CNS) neurons has been partly attributed to the former's intrinsic capacity to initiate and sustain the functionality of a new growth cone. Growth cone generation involves a myriad of processes that centers around the organization of microtubule bundles. Histone deacetylases (HDACs) modulate a wide range of key neuronal processes such as neural progenitor differentiation, learning and memory, neuronal death, and degeneration. HDAC inhibitors have been shown to be beneficial in attenuating neuronal death and promoting neurite outgrowth and axonal regeneration. Recent advances have provided insights on how manipulating HDAC activities, particularly the type II HDACs 5 and 6, which deacetylate tubulin, may benefit axonal regeneration. These advances are discussed herein. J. Cell. Biochem. 115: 1225–1233, 2014. © 2014 Wiley Periodicals, Inc.
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