The midbrain dopaminergic neurons of the substantia nigra and the ventral tegmental area play vital roles in the regulation of voluntary movement, emo-tion and reward in humans. These neurons are highly metabolic and are under constant oxidative stress. The dopaminergic neurons form extensive synaptic projections to the striatum. When these neurons start dying or when their syn-aptic connections fail, humans develop Parkinson´s disease. This disease is ac-companied by the accumulation of toxic α-synuclein-containing protein aggre-gates in nigrostriatal processes. Synucleins accumulate in a majority of healthy nerve terminals in the central nervous system, but what causes the formation of pathological synuclein aggregates is unclear. Recent studies point out that the interface between membrane traffickinin the nerve terminal and the au-tophagy–lysosomal pathway is the site for the aggregate assembly. An urgent goal is to findtherapeutic targets at early stages of the disease when neurons are still functional.