Rho/ROCK Pathway and Noncoding RNAs: Implications in Ischemic Stroke and Spinal Cord Injury

被引:46
作者
Kimura, Tetsu [1 ]
Horikoshi, Yuta [1 ]
Kuriyagawa, Chika [1 ]
Niiyama, Yukitoshi [1 ]
机构
[1] Akita Univ, Dept Anesthesia & Intens Care Med, Grad Sch Med, Akita 0108543, Japan
关键词
stroke; spinal cord injury; Rho; Rho kinase; noncoding RNA; apoptosis; inflammation; axon regrowth; neurogenesis; angiogenesis; RHO-KINASE INHIBITOR; THERAPEUTIC TIME WINDOW; FUNCTIONAL RECOVERY; NEURONAL APOPTOSIS; REPERFUSION INJURY; ENDOTHELIAL-CELLS; SIGNALING PATHWAY; TEMPORAL PROFILE; AXON GROWTH; STEM-CELLS;
D O I
10.3390/ijms222111573
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. RhoA is a small GTPase protein that activates a downstream effector, ROCK. The up-regulation of the RhoA/ROCK pathway contributes to neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrogliosis, and axon growth inhibition in IS and SCI. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), were previously considered to be non-functional. However, they have attracted much attention because they play an essential role in regulating gene expression in physiological and pathological conditions. There is growing evidence that ROCK inhibitors, such as fasudil and VX-210, can reduce injury in IS and SCI in animal models and clinical trials. Recently, it has been reported that miRNAs are decreased in IS and SCI, while lncRNAs are increased. Inhibiting the Rho/ROCK pathway with miRNAs alleviates apoptosis, neuroinflammation, oxidative stress, and axon growth inhibition in IS and SCI. Further studies are required to explore the significance of ncRNAs in IS and SCI and to establish new strategies for preventing and treating these devastating diseases.
引用
收藏
页数:16
相关论文
共 138 条
  • [1] Astrocyte-endothelial interactions at the blood-brain barrier
    Abbott, NJ
    Rönnbäck, L
    Hansson, E
    [J]. NATURE REVIEWS NEUROSCIENCE, 2006, 7 (01) : 41 - 53
  • [2] Modulating Astrocyte Transition after Stroke to Promote Brain Rescue and Functional Recovery: Emerging Targets Include Rho Kinase
    Abeysinghe, Hima Charika S.
    Phillips, Ellie L.
    Chin-Cheng, Heung
    Beart, Philip M.
    Roulston, Carli L.
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (03):
  • [3] Targeting noncoding RNAs in disease
    Adams, Brian D.
    Parsons, Christine
    Walker, Lisa
    Zhang, Wen Cai
    Slack, Frank J.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2017, 127 (03) : 761 - 771
  • [4] Rho-Kinase/ROCK: A Key Regulator of the Cytoskeleton and Cell Polarity
    Amano, Mutsuki
    Nakayama, Masanori
    Kaibuchi, Kozo
    [J]. CYTOSKELETON, 2010, 67 (09) : 545 - 554
  • [5] Aggregation of integrins and RhoA activation are required for Thy-1-induced morphological changes in astrocytes
    Avalos, AM
    Arthur, WT
    Schneider, P
    Quest, AFG
    Burridge, K
    Leyton, L
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (37) : 39139 - 39145
  • [6] Characterization of Dysregulated miRNA in Peripheral Blood Mononuclear Cells from Ischemic Stroke Patients
    Bam, Marpe
    Yang, Xiaoming
    Sen, Souvik
    Zumbrun, Elizabeth E.
    Dennis, Lauren
    Zhang, Jiajia
    Nagarkatti, Prakash S.
    Nagarkatti, Mitzi
    [J]. MOLECULAR NEUROBIOLOGY, 2018, 55 (02) : 1419 - 1429
  • [7] Long non-coding RNAs in ischemic stroke
    Bao, Mei-Hua
    Szeto, Vivian
    Yang, Burton B.
    Zhu, Shu-zhen
    Sun, Hong-Shuo
    Feng, Zhong-Ping
    [J]. CELL DEATH & DISEASE, 2018, 9
  • [8] MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004)
    Bartel, David P.
    [J]. CELL, 2007, 131 (04) : 11 - 29
  • [9] Human let-7 stem-loop precursors harbor features of RNase III cleavage products
    Basyuk, E
    Suavet, F
    Doglio, A
    Bordonné, R
    Bertrand, E
    [J]. NUCLEIC ACIDS RESEARCH, 2003, 31 (22) : 6593 - 6597
  • [10] Gender and Stroke Symptoms: A Review of the Current Literature
    Beal, Claudia C.
    [J]. JOURNAL OF NEUROSCIENCE NURSING, 2010, 42 (02) : 80 - 87