Pathological aggregation of alpha-synuclein as Lewy-bodies and neurites is a hallmark of a group of neurodegenerative disorders named alpha-synucleinopathies. It is becoming apparent that alpha-synuclein facilitates presynaptic neuronal function in the brain, and events leading to its aggregation produce marked disruption of neurotransmitter release mechanism. We discuss here the literature related to the function of alpha-synuclein at the neuronal synapse in synucleinopathies brains and corresponding animal models.