title: mTOR signaling in aging and neurodegeneration: At the crossroad between metabolism dysfunction and impairment of autophagy.
abstract: Compelling evidence indicates that the mammalian target of rapamycin (mTOR) signaling pathway is involved in cellular senescence, organismal aging and age-dependent diseases. mTOR is a conserved serine/threonine kinase that is known to be part of two different protein complexes: mTORC1 and mTORC2, which differ in some components and in upstream and downstream signalling. In multicellular organisms, mTOR regulates cell growth and metabolism in response to nutrients, growth factors and cellular energy conditions. Growing studies highlight that disturbance in mTOR signalling in the brain affects multiple pathways including glucose metabolism, energy production, mitochondrial function, cell growth and autophagy. All these events are key players in age-related cognitive decline such as development of Alzheimer disease (AD). The current review discusses the main regulatory roles of mTOR signalling in the brain, in particular focusing on autophagy, glucose metabolism and mitochondrial functions. Targeting mTOR in the CNS can offer new prospective for drug discovery; however further studies are needed for a comprehensive understanding of mTOR, which lies at the crossroads of multiple signals involved in AD etiology and pathogenesis.
authors: Department of Biochemical Sciences, Sapienza University of Rome, Italy. Electronic address: Marzia.perluigi@uniroma1.it.
authors: Marzia
authors: M
authors: Perluigi
authors: Department of Biochemical Sciences, Sapienza University of Rome, Italy.
authors: Fabio
authors: F
authors: Di Domenico
authors: Sanders-Brown Centre of Aging, University of Kentucky, Lexington KY, USA; Department of Chemistry, University of Kentucky, Lexington KY, USA.
authors: D Allan
authors: DA
authors: Butterfield
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D058570:TOR Serine-Threonine Kinases
keywords: Alzheimer disease; Autophagy; Down Syndrome; mTOR