HDACs and Sirtuins Regulate Autophagy Pathways

In vivo neuroprotection by HDAC inhibition has been linked to upregulation of transcription of antioxidant and growth factor proteins, stimulation of neurogenesis [255], and anti-inflammatory effects [256-258]. An anti-inflammatory effect has been achieved by suppression of microglial activation [259], inhibition of pro-inflammatory cytokine expression [260], or NFkB-mediated inflammatory responses. Treatment with HDAC inhibitors also markedly inhibited ischemia-induced p53 overexpression [261, 262]. In an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE), treatment with TSA (2, Fig. 1) activated a transcriptional program that culminated in decreased caspase 3 activity [263]. In HD, treatment of Drosophila mutants expressing Htt with the HDAC inhibitors SAHA or TSA (1 or 2, Fig. 1) suppressed neuronal photoreceptor generation [177]. 

The precise HDAC isoforms involved in HDAC inhibitor-mediated neuroprotection are unclear. Extrapolating from the cardiac field, it is noteworthy that knockdown of HDAC4 reduced infarct size following myocardial ischemia-induced reperfusion 

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