The effect of alpha-synuclein overexpression on the process of cellular energy metabolism in transgenic mouse model

Post-digestion ¹⁸O labeling technique and comparative proteomics are used to carry out a large-scale proteome characterization for α-synuclein overexpression transgene mouse model. Proteins of transgene mice brain were labeled by ¹⁸O, but not for proteins of control. Spectrum Mill software give the specific value of H/L of every protein detected by HPLC/ESI-QTOF, which reflect the difference of protein expression between labeled and unlabeled. According to the results, we can find the changes of protein expression in the brain of transgene mouse models caused by α-synuclein overexpression. In our study, we find that protein expression of different systems has changed, while the most notable is the down-regulation of mitochondria complex I and complex IV, together with the up-regulation of glucolysis and citric acid cycle associated proteins, which suggests the mitochondrial dysfunction and energy metabolism disorder. Overall, the proteome measurements provide a support that α-synuclein overexpression may involve in the mitochondrial dysfunction, affect the energy metabolism and consequently cause the death of dopaminergic neurons in Parkinson's Disease.