title: Mammalian target of rapamycin: hitting the bull's-eye for neurological disorders.
abstract: The mammalian target of rapamycin (mTOR) and its associated cell signaling pathways have garnered significant attention for their roles in cell biology and oncology. Interestingly, the explosion of information in this field has linked mTOR to neurological diseases with promising initial studies. mTOR, a 289 kDa serine/threonine protein kinase, plays an important role in cell growth and proliferation and is activated through phosphorylation in response to growth factors, mitogens, and hormones. Growth factors, amino acids, cellular nutrients, and oxygen deficiency can down-regulate mTOR activity. The function of mTOR signaling is mediated primarily through two mTOR complexes: mTORC1 and mTORC2. mTORC1 initiates cap-dependent protein translation, a rate-limiting step of protein synthesis, through the phosphorylation of the targets eukaryotic initiation factor 4E-binding protein 1 (4EBP1) and p70 ribosomal S6 kinase (p70S6K). In contrast, mTORC2 regulates development of the cytoskeleton and also controls cell survival. Although closely tied to tumorigenesis, mTOR and the downstream signaling pathways are significantly involved in the central nervous system (CNS) with synaptic plasticity, memory retention, neuroendocrine regulation associated with food intake and puberty, and modulation of neuronal repair following injury. The signaling pathways of mTOR also are believed to be a significant component in a number of neurological diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, tuberous sclerosis, neurofibromatosis, fragile X syndrome, epilepsy, traumatic brain injury, and ischemic stroke. Here we describe the role of mTOR in the CNS and illustrate the potential for new strategies directed against neurological disorders.
authors.affiliation: Department of Neurology and Neurosciences, Cancer Center, University of Medicine and Dentistry - New Jersey Medical School, Newark, NJ, USA.
authors.forename: Zhao Zhong
authors.initials: ZZ
authors.lastname: Chong
authors.forename: Yan Chen
authors.initials: YC
authors.lastname: Shang
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhang
authors.forename: Shaohui
authors.initials: S
authors.lastname: Wang
authors.forename: Kenneth
authors.initials: K
authors.lastname: Maiese
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D018797:Cell Cycle Proteins; D002470:Cell Survival; D003599:Cytoskeleton; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019636:Neurodegenerative Diseases / Q000209:etiology*; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism / Q000502:physiology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493245:CRTC2 protein, human; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D011506:Proteins; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D058570:TOR Serine-Threonine Kinases