Fig. 1.

Schematic representation of molecular events and potential therapeutic targets associated with abnormal αSyn in PD. The molecular events that are reduced in PD and/or potentially neuroprotective, or considered to be neurotoxic, are shown in blue, or red arrows and inhibitory lines, respectively. Accumulation of αSyn oligomer, which can be modulated by several post-translational modification(s) of αSyn, leads to reduced neuronal cell viability by inhibiting ER-Golgi trafficking, autophagy, and/or proteasome. Mitochondrial translocation of αSyn induces production of ROS and RNS, further enhancing oxidative/nitrosative modification of αSyn. Oligomerized αSyn species can also be secreted into extracellular space, which might induce inflammatory glial reactions, pore formation on plasma membrane, or transmission to the neighboring neuronal cells to promote Lewy formation and/or cell death. These neurotoxic events can be ameliorated by several ways as indicated (also see the main text)