mTOR: A Novel Therapeutic Target for Diseases of Multiple Systems

被引:13
作者
Chong, Zhao Zhong [1 ,2 ]
机构
[1] Univ Illinois, Dept Anesthesiol, Chicago, IL 60064 USA
[2] Shandong Acad Med Sci, Inst Mat Med, Jinan 250062, Peoples R China
关键词
Akt; cardiovascular disease; diabetes mellitus; mTOR; neurodegenerative disease; CELL-CYCLE PROGRESSION; RICH AKT SUBSTRATE; P70; S6; KINASE; CHRONIC ALLOGRAFT NEPHROPATHY; RIBOSOMAL-PROTEIN S6; RAPAMYCIN COMPLEX 2; FLUID STEM-CELLS; 40 KDA PRAS40; MAMMALIAN TARGET; TUBEROUS SCLEROSIS;
D O I
10.2174/1389450116666150408103448
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Significant progress in the research of mammalian target of rapamycin (mTOR) in recent years, has greatly enhanced our understanding of the role and cellular pathways through which mTOR control cellular processes, such as translational initiation, actin organization, cell proliferation, and cell survival. mTOR is activated by phosphorylation and functions mainly through mTOR complex 1 or mTOR complex 2. mTORC1 is activated through tuberous sclerosis complex 1/2 dependent and independent mechanisms following the stimulation by growth factors, nutrient, amino acids, and other signaling pathways. The activity of mTOR is closely associated with cell proliferation and differentiation, apoptosis, and autophagy. Activation of mTOR prevents the induction of both apoptosis and autophagy through regulating its multiple targets. Given that the activity of mTOR has been involved in the pathogenesis of neurodegenerative disorders, cardiovascular abnormalities, metabolic diseases, renal transplantation, autoimmune abnormalities, and cancer, manipulating mTOR activation may represent as an innovative therapeutic strategy for these diseases. Yet, the role of mTOR in the body is complicated and therefore, its activity needs to be tightly regulated to achieve beneficial outcome in a specific pathological condition.
引用
收藏
页码:1107 / 1132
页数:26
相关论文
共 341 条
[1]   Lhermitte-Duclos disease: A report of 31 cases with immunohistochemical analysis of the PTEN/AKT/mTOR pathway [J].
Abel, TW ;
Baker, SJ ;
Fraser, MM ;
Tihan, T ;
Nelson, JS ;
Yachnis, AT ;
Bouffard, JP ;
Mena, H ;
Burger, PC ;
Eberhart, CG .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2005, 64 (04) :341-349
[2]  
Abraham RT, 2004, CURR TOP MICROBIOL I
[3]   Site-Specific mTOR Phosphorylation Promotes mTORC1-Mediated Signaling and Cell Growth [J].
Acosta-Jaquez, Hugo A. ;
Keller, Jennifer A. ;
Foster, Kathryn G. ;
Ekim, Bilgen ;
Soliman, Ghada A. ;
Feener, Edward P. ;
Ballif, Bryan A. ;
Fingar, Diane C. .
MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (15) :4308-4324
[4]   Rictor regulates cell migration by suppressing RhoGDI2 [J].
Agarwal, N. K. ;
Chen, C-H ;
Cho, H. ;
Boulbes, D. R. ;
Spooner, E. ;
Sarbassov, D. D. .
ONCOGENE, 2013, 32 (20) :2521-2526
[5]   Integrity of mTORC2 is dependent on the rictor Gly-934 site [J].
Aimbetov, R. ;
Chen, C-H ;
Bulgakova, O. ;
Abetov, D. ;
Bissenbaev, A. K. ;
Bersimbaev, R. I. ;
Sarbassov, D. D. .
ONCOGENE, 2012, 31 (16) :2115-2120
[6]   Rapamycin regulates the phosphorylation of rictor [J].
Akcakanat, Argun ;
Singh, Gopal ;
Hung, Mien-Chie ;
Meric-Bernstam, Funda .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 362 (02) :330-333
[7]   Prognostic role of p-mTOR expression in cancer tissues and metastatic lymph nodes in pT2b gastric cancer [J].
An, Ji Yeong ;
Kim, Kyoung Mee ;
Choi, Min Gew ;
Noh, Jae Hyung ;
Sohn, Tae Sung ;
Bae, Jae Moon ;
Kim, Sung .
INTERNATIONAL JOURNAL OF CANCER, 2010, 126 (12) :2904-2913
[8]   Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease [J].
An, WL ;
Cowburn, RF ;
Li, L ;
Braak, H ;
Alafuzoff, I ;
Iqbal, K ;
Iqbal, IG ;
Winblad, B ;
Pei, JJ .
AMERICAN JOURNAL OF PATHOLOGY, 2003, 163 (02) :591-607
[9]   Transplanted glial scar impedes olfactory bulb reinnervation [J].
Anders, JJ ;
Hurlock, JA .
EXPERIMENTAL NEUROLOGY, 1996, 142 (01) :144-150
[10]   Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1 cyclin B [J].
Astrinidis, A ;
Senapedis, W ;
Coleman, TR ;
Henske, EP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (51) :51372-51379