In recent years, the neuroprotective effects of MPC inhibition have been intensively studied using various models of neurodegenerative diseases. It turned out that a new generation of insulin sensitizers inhibits MPC, and their application for the treatment of AD and PD in multiple cell and animal models showed a decrease in neurodegeneration. In our studies, we wanted to find out whether genetic inhibition of MPC selectively in astrocytes and dopaminergic neurons can have neuroprotective function in the mouse AD and PD models, respectively. Our results of the behavioral assessment showed a significant increase in anxiety in 3xTgAD mice without MPC1, suggesting that metabolic changes caused by inhibition of MPC may contribute to the progression of AD. Selective depletion of MPC1 in DA neurons significantly impacted the behavior of animals at the Pole test, and also affected the number of TH+ cells in VTA. These results can contribute to the knowledge of the energy metabolism of astrocytes in pathological conditions, as well as can provide new insights for the development of treatment for PD.