Taken together, these observations indicate HDAC6 as a master regulator of different neuroprotective mechanisms, partly mediated by controlling MTOC biogenesis and function, [23] and predict a role for defective HDAC6 in neurodegeneration, particularly in MND [26]. As for mammalian models, although a first strain of HDAC6 knockout (KO) mice presented no sign of neurodegeneration, [29] altered emotional behaviors suggested a contribution of HDAC6 to maintain proper neuronal activity [30]. Moreover, a second KO HDAC6 strain displayed ubiquitin-positive aggregates and increased apoptosis of brain nerve cells, both hallmarks of neurodegeneration, starting from 6 months of age [31]. These and other results suggest for HDAC6 a complex role in contributing to either neuroprotection or neurodegeneration, depending on the specific pathological condition [7,26,32]. These opposite effects can indeed hamper the development of therapeutic strategies based on HDAC6 modulation [7].