Mammalian target of rapamycin complexes

Novel targets to arrest neurodegeneration in several dementing conditions involving misfolded protein accumulations may be found in the diverse signaling pathways of the mammalian (or mechanistic) target of rapamycin (mTOR). 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. It also plays a role in the cerebrovascular dysfunction of AD. mTOR is a serine kinase residing in either of two complexes, mTORC1 and mTORC2. New data suggest that their balanced actions also have implications for Parkinson's and Huntington's diseases, frontotemporal dementia, and amyotrophic lateral sclerosis. Beyond rapamycin, rapalogs having lesser toxicity hold promise in arresting these age-dependent conditions.