Figure 2.

A hypothetical model for secretion and synaptic targets of α-synuclein oligomers. The figure shows four different mechanisms for unconventional secretion of α-synuclein (Nickel and Rabouille, 2009). Mechanism 1 depicts a non-vesicular translocation of α-synuclein mediated by an unknown transmembrane protein located at the plasma membrane. Mechanisms 2–4 depict vesicular mechanisms for α-synuclein secretion that involve lysosomes (2), microvesicle shedding (3), or endosome/multivesicular bodies (4). Mechanisms 3 and 4 involve the release of α-synuclein into exosomes. Once in the extracellular space (Lee, 2008), α-synuclein oligomers can be removed by proteolytic degradation (A) or endocytocis (C) (Desplats et al., 2009). The accumulation of α-synuclein in the extracellular space can activate microglia (D) or alter the plasma membrane through the formation of pore/perforations (B) that can deregulate calcium and metal transition homeostasis (Danzer et al., 2007).