Fig. 4

mTOR inhibition in neurodegenerative disorders. As a nutrient sensor, mTOR has important homeostatic functions to regulate energy metabolism and support neuronal growth and plasticity. However, in Alzheimer’s disease (AD), mTOR alternately plays important pathogenic roles by inhibiting both insulin signaling and autophagic removal of beta amyloid and Tau aggregates. Overactive mTOR also abets the cerebrovascular dysfunction of AD. Some of the other neurodegeneration conditions, discussed herein, have similar proteotoxic mechanisms (indicated in parentheses). The beneficial actions of mTOR inhibition with rapamycin are shown as arrows to the corresponding bulleted effects. Dashed arrows indicate unproven actions on those proteotoxic processes