AKT1 and Parkinson disease: Metformin may treat PD symptoms through the following mechanisms: (1) metformin-induced protein kinase B activation may activate nuclear factor Nrf2/heme-oxygenase-1 pathway to ameliorate mitochondrial dysfunction and energy deficit [247,248], (2) metformin may reduce inflammation by suppressing microglial activation and decreasing proinflammatory cytokines (TNF- and IL-1) [249,250,251], (3) metformin may prevent dopaminergic neuron loss [250,251], (4) Metformin may inhibit α-synuclein phosphorylation [252].