ATP depletion is the major cause of MPP⁺ induced dopamine neuronal death and worm lethality in α-synuclein transgenic C. elegans

Objective: To investigate the toxic effect of environmental neurotoxin MPP⁺ to C. elegans and identify the mechanisms that cause the toxicity. Methods: Human α-synuclein transgenic C. elegans was used as the animal model, the toxic effect of MPP⁺ to dopamine (DA) neurons and the lifespan of worms was tested. The worms were feed with OP50 to determine whether ATP increase can rescue the worm from toxicity. ATP level and aberrant protein accumulation were analyzed in the MPP⁺ treated worms with or without OP50 addition. Results: We found that MPP⁺ induced DA cell death and worm lethality, which could be prevented by OP50 treatment. OP50 exerted the protective effect by up-regulating ATP level, even though it also induced accumulation of α-synuclein. Despite the undefined role of protein aggregation to the cell death, our results showed that the toxicity of MPP ⁺ was mainly caused by the ATP depletion in the α-synuclein transgenic C. elegans. Conclusion: MPP⁺ could induce DA neuronal death and worm lethality in α-synuclein transgenic C. elegans; Compared with the aggregation of α-synuclein, the major cause of MPP⁺ toxicity appeared due to ATP depletion.