title: The rationale of targeting mammalian target of rapamycin for ischemic stroke.
abstract: Given the current limitation of therapeutic approach for ischemic stroke, a leading cause of disability and mortality in the developed countries, to develop new therapeutic strategies for this devastating disease is urgently necessary. As a serine/threonine kinase, mammalian target of rapamycin (mTOR) activation can mediate broad biological activities that include protein synthesis, cytoskeleton organization, and cell survival. mTOR functions through mTORC1 and mTORC2 complexes and their multiple downstream substrates, such as eukaryotic initiation factor 4E-binding protein 1, p70 ribosomal S6 kinase, sterol regulatory element-binding protein 1, hypoxia inducible factor-1, and signal transducer and activator transcription 3, Yin Ying 1, Akt, protein kinase c-alpha, Rho GTPase, serum-and gucocorticoid-induced protein kinase 1, etc. Specially, the role of mTOR in the central nervous system has been attracting considerable attention. Based on the ability of mTOR to prevent neuronal apoptosis, inhibit autophagic cell death, promote neurogenesis, and improve angiogenesis, mTOR may acquire the capability of limiting the ischemic neuronal death and promoting the neurological recovery. Consequently, to regulate the activity of mTOR holds a potential as a novel therapeutic strategy for ischemic stroke.
authors.affiliation: Department of Neurology and Neurosciences, Cancer Center, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07101, USA. chongzh@umdnj.edu
authors.forename: Zhao Zhong
authors.initials: ZZ
authors.lastname: Chong
authors.forename: Qingqiang
authors.initials: Q
authors.lastname: Yao
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D020520:Brain Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D055495:Neurogenesis; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus