Indeed, some of the reported failures or unexpected outcomes in preclinical models of experimental PD treated with the previously identified neuroprotective agents in vivo (best exemplified by SHH signaling, section 4.1.2) might be directly related to the neglect of this complexity and the far-reaching interactions between mDA neurons and their efferent outputs as well as afferent inputs. This evidence concerns the gene SHH and Parkinson disease.