Literature DB >> 22895182

The role of mTOR signaling pathway in spinal cord injury.

Haruo Kanno1, Hiroshi Ozawa, Akira Sekiguchi, Seiji Yamaya, Satoshi Tateda, Kenichiro Yahata, Eiji Itoi.   

Abstract

The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in multiple cellular functions, such as cell metabolism, proliferation and survival. Many previous studies have shown that mTOR regulates both neuroprotective and neuroregenerative functions in trauma and various diseases in the central nervous system (CNS). Recently, we reported that inhibition of mTOR using rapamycin reduces neural tissue damage and locomotor impairment after spinal cord injury (SCI) in mice. Our results demonstrated that the administration of rapamycin at four hours after injury significantly increases the activity of autophagy and reduces neuronal loss and cell death in the injured spinal cord. Furthermore, rapamycin-treated mice show significantly better locomotor function in the hindlimbs following SCI than vehicle-treated mice. These findings indicate that the inhibition of mTOR signaling using rapamycin during the acute phase of SCI produces neuroprotective effects and reduces secondary damage at lesion sites. However, the role of mTOR signaling in injured spinal cords has not yet been fully elucidated. Various functions are regulated by mTOR signaling in the CNS, and multiple pathophysiological processes occur following SCI. Here, we discuss several unresolved issues and review the evidence from related articles regarding the role and mechanisms of the mTOR signaling pathway in neuroprotection and neuroregeneration after SCI.

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Year:  2012        PMID: 22895182      PMCID: PMC3466516          DOI: 10.4161/cc.21262

Source DB:  PubMed          Journal:  Cell Cycle        ISSN: 1551-4005            Impact factor:   4.534


  76 in total

1.  Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor.

Authors:  Markus Guba; Philipp von Breitenbuch; Markus Steinbauer; Gudrun Koehl; Stefanie Flegel; Matthias Hornung; Christiane J Bruns; Carl Zuelke; Stefan Farkas; Matthias Anthuber; Karl-Walter Jauch; Edward K Geissler
Journal:  Nat Med       Date:  2002-02       Impact factor: 53.440

2.  Phase II trial of temsirolimus in patients with metastatic breast cancer.

Authors:  Gini F Fleming; Cynthia X Ma; Dezheng Huo; Husain Sattar; Maria Tretiakova; L Lin; Olwen M Hahn; F O Olopade; R Nanda; Philip C Hoffman; M J Naughton; Timothy Pluard; Suzanne D Conzen; Matthew J Ellis
Journal:  Breast Cancer Res Treat       Date:  2012-01-13       Impact factor: 4.872

Review 3.  Updates of mTOR inhibitors.

Authors:  Hongyu Zhou; Yan Luo; Shile Huang
Journal:  Anticancer Agents Med Chem       Date:  2010-09       Impact factor: 2.505

Review 4.  mTOR signaling and drug development in cancer.

Authors:  Janet Dancey
Journal:  Nat Rev Clin Oncol       Date:  2010-03-16       Impact factor: 66.675

5.  Rapamycin confers preconditioning-like protection against ischemia-reperfusion injury in isolated mouse heart and cardiomyocytes.

Authors:  Shakil Khan; Fadi Salloum; Anindita Das; Lei Xi; George W Vetrovec; Rakesh C Kukreja
Journal:  J Mol Cell Cardiol       Date:  2006-08       Impact factor: 5.000

Review 6.  Emerging roles for mammalian target of rapamycin inhibitors in the treatment of solid tumors and hematological malignancies.

Authors:  Nushmia Z Khokhar; Jessica K Altman; Leonidas C Platanias
Journal:  Curr Opin Oncol       Date:  2011-11       Impact factor: 3.645

7.  Increased oxidative-related mechanisms in the spinal cord injury in old rats.

Authors:  Tiziana Genovese; Emanuela Mazzon; Rosanna Di Paola; Concetta Crisafulli; Carmelo Muià; Placido Bramanti; Salvatore Cuzzocrea
Journal:  Neurosci Lett       Date:  2005-10-17       Impact factor: 3.046

8.  Inhibition of mTOR signaling in Parkinson's disease prevents L-DOPA-induced dyskinesia.

Authors:  Emanuela Santini; Myriam Heiman; Paul Greengard; Emmanuel Valjent; Gilberto Fisone
Journal:  Sci Signal       Date:  2009-07-21       Impact factor: 8.192

9.  Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease.

Authors:  Brinda Ravikumar; Coralie Vacher; Zdenek Berger; Janet E Davies; Shouqing Luo; Lourdes G Oroz; Francesco Scaravilli; Douglas F Easton; Rainer Duden; Cahir J O'Kane; David C Rubinsztein
Journal:  Nat Genet       Date:  2004-05-16       Impact factor: 38.330

Review 10.  Immunoregulatory functions of mTOR inhibition.

Authors:  Angus W Thomson; Hēth R Turnquist; Giorgio Raimondi
Journal:  Nat Rev Immunol       Date:  2009-05       Impact factor: 53.106

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  41 in total

1.  Mammalian target of rapamycin's distinct roles and effectiveness in promoting compensatory axonal sprouting in the injured CNS.

Authors:  Do-Hun Lee; Xueting Luo; Benjamin J Yungher; Eric Bray; Jae K Lee; Kevin K Park
Journal:  J Neurosci       Date:  2014-11-12       Impact factor: 6.167

2.  Anti-inflammatory effects of Metformin improve the neuropathic pain and locomotor activity in spinal cord injured rats: introduction of an alternative therapy.

Authors:  Khashayar Afshari; Amir Dehdashtian; Nazgol-Sadat Haddadi; Arvin Haj-Mirzaian; Arad Iranmehr; Mohammad Ali Ebrahimi; Seyed Mohammad Tavangar; Hedyeh Faghir-Ghanesefat; Fatemeh Mohammadi; Nastaran Rahimi; Abbas Norouzi Javidan; Ahmad Reza Dehpour
Journal:  Spinal Cord       Date:  2018-06-29       Impact factor: 2.772

3.  Metformin Improves Functional Recovery After Spinal Cord Injury via Autophagy Flux Stimulation.

Authors:  Di Zhang; Jun Xuan; Bin-Bin Zheng; Yu-Long Zhou; Yan Lin; Yao-Sen Wu; Yi-Fei Zhou; Yi-Xing Huang; Quan Wang; Li-Yan Shen; Cong Mao; Yan Wu; Xiang-Yang Wang; Nai-Feng Tian; Hua-Zi Xu; Xiao-Lei Zhang
Journal:  Mol Neurobiol       Date:  2016-05-11       Impact factor: 5.590

Review 4.  CRISPR, Prime Editing, Optogenetics, and DREADDs: New Therapeutic Approaches Provided by Emerging Technologies in the Treatment of Spinal Cord Injury.

Authors:  Vera Paschon; Felipe Fernandes Correia; Beatriz Cintra Morena; Victor Allisson da Silva; Gustavo Bispo Dos Santos; Maria Cristina Carlan da Silva; Alexandre Fogaça Cristante; Stephanie Michelle Willerth; Florence Evelyne Perrin; Alexandre Hiroaki Kihara
Journal:  Mol Neurobiol       Date:  2020-01-11       Impact factor: 5.590

5.  Inhibition of the Ras/Raf/ERK1/2 Signaling Pathway Restores Cultured Spinal Cord-Injured Neuronal Migration, Adhesion, and Dendritic Spine Development.

Authors:  Dongdong Xu; Fujiang Cao; Shiwei Sun; Tao Liu; Shiqing Feng
Journal:  Neurochem Res       Date:  2016-04-21       Impact factor: 3.996

6.  Suppression of mTOR signaling pathway promotes bone marrow mesenchymal stem cells differentiation into osteoblast in degenerative scoliosis: in vivo and in vitro.

Authors:  Yu Wang; Xiao-Dong Yi; Chun-De Li
Journal:  Mol Biol Rep       Date:  2016-11-25       Impact factor: 2.316

7.  KU0063794, a Dual mTORC1 and mTORC2 Inhibitor, Reduces Neural Tissue Damage and Locomotor Impairment After Spinal Cord Injury in Mice.

Authors:  Marika Cordaro; Irene Paterniti; Rosalba Siracusa; Daniela Impellizzeri; Emanuela Esposito; Salvatore Cuzzocrea
Journal:  Mol Neurobiol       Date:  2016-03-10       Impact factor: 5.590

8.  Exendin-4 Enhances Motor Function Recovery via Promotion of Autophagy and Inhibition of Neuronal Apoptosis After Spinal Cord Injury in Rats.

Authors:  Hao-Tian Li; Xing-Zhang Zhao; Xin-Ran Zhang; Gang Li; Zhi-Qiang Jia; Ping Sun; Ji-Quan Wang; Zhong-Kai Fan; Gang Lv
Journal:  Mol Neurobiol       Date:  2015-07-22       Impact factor: 5.590

Review 9.  The role of Wnt/mTOR signaling in spinal cord injury.

Authors:  Peng Cheng; Hai-Yang Liao; Hai-Hong Zhang
Journal:  J Clin Orthop Trauma       Date:  2022-01-04

Review 10.  The metabolic syndrome and neuropathy: therapeutic challenges and opportunities.

Authors:  Brian Callaghan; Eva Feldman
Journal:  Ann Neurol       Date:  2013-09       Impact factor: 10.422

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