Cells and Diseases Targeted by HDACi

Systemic administration of HDACi can potentially affect many, if not all, cells of the body depending upon whether a given agent can cross the blood-brain barrier. Some HDACi, such as valproic acid but typically not the hydroxamates, such as TsA, do cross the blood-brain barrier. Indeed, valproic and certain newer antiepileptic agents may exert their effects by inhibition of HDAC activity and differential effects on excitatory and inhibitory neuronal activities (Hoffmann et al. 2008; Fukuchi et al. 2009; Eyal et al. 2004). However, with regard to HDACi-associated modulation of inflammatory responses, the precise sites of actions, cellular targets and mechanisms of action are not well understood, with a considerable number of in vitro and in vivo studies offering complex, incomplete, and sometimes contradictory data-sets. Resolution of this problem may take a long time, given the divergent approaches of scientists ranging from studies of the effects of an HDACi on cells in vitro (Table 1) to assessment in whole animals and complex disease models (Table 2).

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