Hypothesis: Alpha-synuclein loss-of-function as a contributor to parkinsonian pathology. Our findings suggest that the region-specific degeneration of ventral midbrain dopamine neurons characteristic of Parkinson's disease that is widely attributed to accumulation of toxic aggregates of alpha-synuclein can be accurately reproduced by knockdown of endogenous alpha-synuclein. These differing paths to degeneration converge upon displacement of alpha-synuclein from its natural location at synaptic terminals.