Figure 1. Mechanisms of pesticide-induced SNc dopamine neurodegeneration.

(A) Paraquat (PQ) enters the organism in its native divalent cation state, PQ²⁺, which cannot cross the plasma membrane. However, conversion to PQ⁺ by a reducing agent enables PQ⁺ to selectively enter DA neurons via the dopamine transporter (DAT)³⁴. PQ⁺ accumulates in neurons where it induces increased ROS generation and α-synuclein aggregation³⁵. Resulting oxidative stress contributes to SNc DA neurodegeneration. (B) Rotenone is lipophilic and freely crosses the membrane via passive diffusion³⁶. Rotenone then induces ROS buildup and neurotoxic oxidative stress via direct inhibition of Complex I of the mitochondrial electron transport chain (ETC)²⁵.