Fig. 4

Hypothetical mechanism for α-synuclein mediated complement-dependent cytotoxicity. Intracellular α-synuclein (α-syn) stress, excretion of α-syn-covered extracellular vesicles, or binding of extracellular α-syn to the cell surface leads to the presentation of α-syn at the plasma membrane. Here, α-syn could potentially activate the classical complement cascade by direct binding of C1 leading to deposition of C4b, production of anaphylatoxins, C3a opsonization, and the formation of the membrane attack complex (MAC). Complement inhibitors, exemplified by Cp20 and RACI, holds neuroprotective potential by making the cell inert to the binding of C1q to membrane-associated α-syn