Aim αsynuclein genes including its mutations, duplication and triplication are the first identified genetic factor involved in the progress of PD.And αsynuclein (tsyn) is the main component in pathological hallmark of PD, termed as Lewy bodies (LB).Methods Human wildtype osyn was stereotactic injected through rAAV2/1 vectors in the bilateral SN of mouse and examined the effects for up to 12 weeks.Results Delivery of rAAV2/1αsyn caused significant SN degeneration accompanied with appearance of dystrophic striatal neurites,loss of nigral dopaminergic (DA) neurons and dissolving nigral neuron bodies in a timedependent manner.In addition, the αsyn overexpressed mice also developed significant deficits in locomotor function at 12 weeks when the loss of DA neurons exceeded a threshold of 50%.To investigate the sensitivity to MPTP in αsynoverexpressed mice, mice that were treated with rAAV for 8 weeks were injected with MPTP for five subsequent days.The insults on DA neuronal loss, striatal dopamine depletion, dopamine turnover and locomotor dysfunction were significantly increased compared with mice without αsyn overexpression.Furthermore, increased phosphorylation (S129) was accumulation and after the combined insults.Conclusions The overexpressed αsyn induces progressive nigrostriatal degeneration and increases the sensitivity of DA neurons to MPTP.And the targeted overexpression of αsyn and the combination with environmental toxins may provide valuable models for PD researches.