473
Views
36
CrossRef citations to date
0
Altmetric
Review

ROCK as a therapeutic target for ischemic stroke

, &
Pages 1167-1177 | Received 24 Aug 2017, Accepted 19 Oct 2017, Published online: 30 Oct 2017

References

  • Mozaffarian D, Benjamin EJ, Go AS et al. Heart disease and stroke statistics-2016 update: A report from the American Heart Association. Circulation. 2016;133(4):e38-360.
  • Solomon NA, Glick HA, Russo CJ, et al. Patient preferences for stroke outcomes. Stroke. 1994 Sep;25(9):1721–1725.
  • Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017 Mar 07;135(10):e146–e603.
  • del Zoppo GJ. The neurovascular unit in the setting of stroke. J Intern Med. 2010 Feb;267(2):156–171.
  • Nakagawa O, Fujisawa K, Ishizaki T, et al. ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice. FEBS Lett. 1996 Aug 26;392(2):189–193.
  • Leung T, Manser E, Tan L, et al. A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes. J Biol Chem. 1995 Dec 8;270(49):29051–29054.
  • Matsui T, Amano M, Yamamoto T, et al. Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J. 1996 May 1;15(9):2208–2216.
  • Takahashi K, Sasaki T, Mammoto A, et al. Interaction of radixin with Rho small G protein GDP/GTP exchange protein Dbl. Oncogene. 1998 Jun 25;16(25):3279–3284.
  • Ishizaki T, Maekawa M, Fujisawa K, et al. The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO J. 1996 Apr 15;15(8):1885–1893.
  • Leung T, Chen XQ, Manser E, et al. The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton. Mol Cell Biol. 1996 Oct;16(10):5313–5327.
  • Amano M, Chihara K, Nakamura N, et al. The COOH terminus of Rho-kinase negatively regulates rho-kinase activity. J Biol Chem. 1999 Nov 5;274(45):32418–32424.
  • Garg R, Riento K, Keep N, et al. N-terminus-mediated dimerization of ROCK-I is required for RhoE binding and actin reorganization. Biochem J. 2008 Apr 15;411(2):407–414.
  • Jacobs M, Hayakawa K, Swenson L, et al. The structure of dimeric ROCK I reveals the mechanism for ligand selectivity. J Biol Chem. 2006 Jan 6;281(1):260–268.
  • Sin WC, Chen XQ, Leung T, et al. RhoA-binding kinase alpha translocation is facilitated by the collapse of the vimentin intermediate filament network. Mol Cell Biol. 1998 Nov;18(11):6325–6339.
  • Chen XQ, Tan I, Ng CH, et al. Characterization of RhoA-binding kinase ROKalpha implication of the pleckstrin homology domain in ROKalpha function using region-specific antibodies. J Biol Chem. 2002 Apr 12;277(15):12680–12688.
  • Kimura K, Fukata Y, Matsuoka Y, et al. Regulation of the association of adducin with actin filaments by Rho-associated kinase (Rho-kinase) and myosin phosphatase. J Biol Chem. 1998 Mar 6;273(10):5542–5548.
  • Inada H, Togashi H, Nakamura Y, et al. Balance between activities of Rho kinase and type 1 protein phosphatase modulates turnover of phosphorylation and dynamics of desmin/vimentin filaments. J Biol Chem. 1999 Dec 3;274(49):34932–34939.
  • Pelosi M, Marampon F, Zani BM, et al. ROCK2 and its alternatively spliced isoform ROCK2m positively control the maturation of the myogenic program. Mol Cell Biol. 2007 Sep;27(17):6163–6176.
  • Smith AL, Dohn MR, Brown MV, et al. Association of Rho-associated protein kinase 1 with E-cadherin complexes is mediated by p120-catenin. Mol Biol Cell. 2012 Jan;23(1):99–110.
  • Chevrier V, Piel M, Collomb N, et al. The Rho-associated protein kinase p160ROCK is required for centrosome positioning. J Cell Biol. 2002 May 27;157(5):807–817. 12034773.
  • Farber MJ, Rizaldy R, Hildebrand JD. Shroom2 regulates contractility to control endothelial morphogenesis. Mol Biol Cell. 2011 Mar 15;22(6):795–805.
  • Boureux A, Vignal E, Faure S, et al. Evolution of the Rho family of ras-like GTPases in eukaryotes. Mol Biol Evol. 2007 Jan;24(1):203–216.
  • Coleman ML, Sahai EA, Yeo M, et al. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat Cell Biol. 2001 Apr;3(4):339–345.
  • Sebbagh M, Renvoize C, Hamelin J, et al. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol. 2001 Apr;3(4):346–352.
  • Amano M, Nakayama M, Kaibuchi K. Rho-kinase/ROCK: a key regulator of the cytoskeleton and cell polarity. Cytoskeleton (Hoboken, NJ). 2010 Sep;67(9):545–554.
  • Schofield AV, Bernard O. Rho-associated coiled-coil kinase (ROCK) signaling and disease. Crit Rev Biochem Mol Biol. 2013 Jul-Aug;48(4):301–316.
  • Julian L, Olson MF. Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases. 2014;5:e29846.
  • Kang JH, Jiang Y, Toita R, et al. Phosphorylation of Rho-associated kinase (Rho-kinase/ROCK/ROK) substrates by protein kinases A and C. Biochimie. 2007 Jan;89(1):39–47.
  • Riou P, Kjaer S, Garg R, et al. 14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G proteins. Cell. 2013 Apr 25;153(3):640–653.
  • Thumkeo D, Watanabe S, Narumiya S. Physiological roles of Rho and Rho effectors in mammals. Eur J Cell Biol. 2013 Oct-Nov;92(10–11):303–315.
  • Knipe RS, Tager AM, Liao JK. The Rho kinases: critical mediators of multiple profibrotic processes and rational targets for new therapies for pulmonary fibrosis. Pharmacol Rev. 2015;67(1):103–117.
  • Tanaka T, Nishimura D, Wu RC, et al. Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase. J Biol Chem. 2006 Jun 2;281(22):15320–15329.
  • Koch JC, Tonges L, Barski E, et al. ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS. Cell Death Dis. 2014;5:e1225.
  • Forgione N, Fehlings MG. Rho-ROCK inhibition in the treatment of spinal cord injury. World Neurosurg. 2014 Sep-Oct;82(3–4):e535–e539.
  • Fournier AE, Takizawa BT, Strittmatter SM. Rho kinase inhibition enhances axonal regeneration in the injured CNS. J Neuroscience. 2003 Feb 15;23(4):1416–1423.
  • Boato F, Hendrix S, Huelsenbeck SC, et al. C3 peptide enhances recovery from spinal cord injury by improved regenerative growth of descending fiber tracts. J Cell Sci. 2010 May 15;123(Pt 10):1652–1662.
  • Rikitake Y, Kim HH, Huang Z, et al. Inhibition of Rho kinase (ROCK) leads to increased cerebral blood flow and stroke protection. Stroke. 2005 Oct;36(10):2251–2257.
  • Wang QM, Stalker TJ, Gong Y, et al. Inhibition of Rho-kinase attenuates endothelial-leukocyte interaction during ischemia-reperfusion injury. Vasc Med. 2012 Dec;17(6):379–385.
  • Hyun LJ, Zheng Y, von Bornstadt D, et al. Selective ROCK2 inhibition in focal cerebral ischemia. Ann Clin Translational Neurol. 2014 Jan;1(1):2–14.
  • Shibuya M, Hirai S, Seto M, et al. Effects of fasudil in acute ischemic stroke: results of a prospective placebo-controlled double-blind trial. J Neurol Sci. 2005 Nov 15;238(1–2):31–39. PubMed PMID: 16005902.
  • Feske SK, Sorond FA, Henderson GV, et al. Increased leukocyte ROCK activity in patients after acute ischemic stroke. Brain Res. 2009 Feb 27;1257:89–93.
  • Stoll G, Kleinschnitz C, Nieswandt B. Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood. 2008 Nov 1;112(9):3555–3562.
  • Suzuki A, Shin JW, Wang Y, et al. RhoA is essential for maintaining normal megakaryocyte ploidy and platelet generation [Research Support, N.I.H., Extramural]. PloS One. 2013;8(7):e69315.
  • Pleines I, Hagedorn I, Gupta S, et al. Megakaryocyte-specific RhoA deficiency causes macrothrombocytopenia and defective platelet activation in hemostasis and thrombosis. Blood. 2012 Jan 26;119(4):1054–1063.
  • Klages B, Brandt U, Simon MI, et al. Activation of G12/G13 results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. J Cell Biol. 1999 Feb 22;144(4):745–754.
  • Sladojevic N, Oh GT, Kim HH, et al. Decreased thromboembolic stroke but not atherosclerosis or vascular remodeling in mice with ROCK2-deficient platelets. Cardiovasc Res. 2017 Apr 14.
  • Magnus T, Wiendl H, Kleinschnitz C. Immune mechanisms of stroke. Curr Opin Neurol. 2012 Jun;25(3):334–340.
  • Laufs U, Liao JK. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem. 1998 Sep 11;273(37):24266–24271.
  • Satoh S, Kobayashi T, Hitomi A, et al. Inhibition of neutrophil migration by a protein kinase inhibitor for the treatment of ischemic brain infarction. Jpn J Pharmacol. 1999 May;80(1):41–48.
  • Satoh S, Utsunomiya T, Tsurui K, et al. Pharmacological profile of hydroxy fasudil as a selective rho kinase inhibitor on ischemic brain damage. Life Sci. 2001 Aug 10;69(12):1441–1453.
  • Hara M, Takayasu M, Watanabe K, et al. Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats. J Neurosurg. 2000 Jul;93(1 Suppl):94–101.
  • Liu Z, Fan Y, Won SJ, et al. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke. 2007 Jan;38(1):146–152.
  • Brecht S, Schwarze K, Waetzig V, et al. Changes in peptidyl-prolyl cis/trans isomerase activity and FK506 binding protein expression following neuroprotection by FK506 in the ischemic rat brain. Neuroscience. 2003;120(4):1037–1048.
  • Wei Y, Yemisci M, Kim HH, et al. Fingolimod provides long-term protection in rodent models of cerebral ischemia. Ann Neurol. 2011 Jan;69(1):119–129.
  • Kipnis J, Yoles E, Porat Z, et al. T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: possible therapy for optic neuropathies. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7446–7451.
  • Ochs HD, Oukka M, Torgerson TR. TH17 cells and regulatory T cells in primary immunodeficiency diseases. J Allergy Clin Immunol. 2009 May;123(5):977-983; quiz 984-985.
  • Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010 May;87(5):779–789.
  • Kim ES, Kim RS, Ren RF, et al. Transforming growth factor-beta inhibits apoptosis induced by beta-amyloid peptide fragment 25-35 in cultured neuronal cells. Brain Res Mol Brain Res. 1998 Nov 20;62(2):122–130.
  • Nakagawa M, Higuchi I, Yoshidome H, et al. Familial facioscapulohumeral muscular dystrophy: phenotypic diversity and genetic abnormality. Acta Neurol Scand. 1996 Feb-Mar;93(2–3):189–192.
  • Shimada H, Rajagopalan LE. Rho kinase-2 activation in human endothelial cells drives lysophosphatidic acid-mediated expression of cell adhesion molecules via NF-kappaB p65. J Biol Chem. 2010 Apr 23;285(17):12536–12542.
  • Caplan S, Zeliger S, Wang L, et al. Cell-surface-expressed T-cell antigen-receptor zeta chain is associated with the cytoskeleton. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4768–4772.
  • Heasman SJ, Ridley AJ. Multiple roles for RhoA during T cell transendothelial migration. Small GTPases. 2010 Nov;1(3):174–179.
  • Teramoto H, Salem P, Robbins KC, et al. Tyrosine phosphorylation of the vav proto-oncogene product links FcepsilonRI to the Rac1-JNK pathway. J Biol Chem. 1997 Apr 18;272(16):10751–10755.
  • Perona R, Montaner S, Saniger L, et al. Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins. Genes Dev. 1997 Feb 15;11(4):463–475.
  • Biswas PS, Gupta S, Chang E, et al. Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice. J Clin Invest. 2010 Sep;120(9):3280–3295.
  • Allan LM, Rowan EN, Firbank MJ, et al. Long term incidence of dementia, predictors of mortality and pathological diagnosis in older stroke survivors. Brain. 2011 Dec;134(Pt 12):3716–3727.
  • Doyle KP, Quach LN, Sole M. B-lymphocyte-mediated delayed cognitive impairment following stroke. J Neurosci. 2015 Feb 4;35(5):2133–2145.
  • Natkanski E, Lee WY, Mistry B, et al. B cells use mechanical energy to discriminate antigen affinities. Science (New York, NY). 2013 Jun 28;340(6140):1587–1590.
  • McDonald DA, Shi C, Shenkar R, et al. Fasudil decreases lesion burden in a murine model of cerebral cavernous malformation disease. Stroke. 2012 Feb;43(2):571–574.
  • Ding J, Li QY, Wang X, et al. Fasudil protects hippocampal neurons against hypoxia-reoxygenation injury by suppressing microglial inflammatory responses in mice. J Neurochem. 2010 Sep;114(6):1619–1629.
  • Wang HW, Liu PY, Oyama N, et al. Deficiency of ROCK1 in bone marrow-derived cells protects against atherosclerosis in LDLR-/- mice. FASEB J. 2008 Oct;22(10):3561–3570.
  • Matoba K, Kawanami D, Ishizawa S, et al. Rho-kinase mediates TNF-alpha-induced MCP-1 expression via p38 MAPK signaling pathway in mesangial cells. Biochem Biophys Res Commun. 2010 Nov 26;402(4):725–730.
  • Zandi S, Nakao S, Chun KH, et al. ROCK-isoform-specific polarization of macrophages associated with age-related macular degeneration. Cell Rep. 2015 Feb 24;10(7):1173–1186.
  • Barakat R, Redzic Z. The role of activated microglia and resident macrophages in the neurovascular unit during cerebral ischemia: is the jury still out? Med Princ Pract. 2015 Aug 19;25:3–14.
  • Isgro J, Gupta S, Jacek E, et al. Enhanced rho-associated protein kinase activation in patients with systemic lupus erythematosus. Arthritis Rheum. 2013 Jun;65(6):1592–1602.
  • Zanin-Zhorov A, Weiss JM, Nyuydzefe MS, et al. Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16814–16819.
  • Lally L, Pernis A, Narula N, et al. Increased rho kinase activity in temporal artery biopsies from patients with giant cell arteritis. Rheumatology (Oxford, England). 2015 Mar;54(3):554–558.
  • Stamatovic SM, Keep RF, Kunkel SL, et al. Potential role of MCP-1 in endothelial cell tight junction ‘opening’: signaling via Rho and Rho kinase. J Cell Sci. 2003 Nov 15;116(Pt 22):4615–4628.
  • He QW, Xia YP, Chen SC, et al. Astrocyte-derived sonic hedgehog contributes to angiogenesis in brain microvascular endothelial cells via RhoA/ROCK pathway after oxygen-glucose deprivation. Mol Neurobiol. 2013 Jun;47(3):976–987.
  • Tonges L, Koch JC, Bahr M, et al. ROCKing regeneration: rho kinase inhibition as molecular target for neurorestoration. Front Mol Neurosci. 2011;4:39.
  • Tonges L, Frank T, Tatenhorst L, et al. Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson’s disease. Brain. 2012 Nov;135(Pt 11):3355–3370.
  • Yamashita K, Kotani Y, Nakajima Y, et al. Fasudil, a Rho kinase (ROCK) inhibitor, protects against ischemic neuronal damage in vitro and in vivo by acting directly on neurons. Brain Res. 2007 Jun;18(1154):215–224.
  • Ding J, Yu JZ, Li QY, et al. Rho kinase inhibitor Fasudil induces neuroprotection and neurogenesis partially through astrocyte-derived G-CSF. Brain Behav Immun. 2009 Nov;23(8):1083–1088.
  • Shimokawa H, Takeshita A. Rho-kinase is an important therapeutic target in cardiovascular medicine. Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1767–1775.
  • Lohn M, Plettenburg O, Ivashchenko Y, et al. Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. Hypertension. 2009 Sep;54(3):676–683.
  • Williams RD, Novack GD, van Haarlem T, et al. Ocular hypotensive effect of the Rho kinase inhibitor AR-12286 in patients with glaucoma and ocular hypertension. Am J Ophthalmol. 2011 Nov;152(5):834–841.e1.
  • Chen J, Runyan SA, Robinson MR. Novel ocular antihypertensive compounds in clinical trials. Clin Ophthalmol. 2011;5:667–677.
  • O’Brien EC, Greiner MA, Xian Y, et al. Clinical effectiveness of statin therapy after ischemic stroke: primary results from the statin therapeutic area of the patient-centered research into outcomes stroke patients prefer and effectiveness research (PROSPER) study. Circulation. 2015 Oct 13;132(15):1404–1413.
  • Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res. 2017 Jan 06;120(1):229–243.
  • Crouse JR 3rd, Byington RP, Furberg CD. HMG-CoA reductase inhibitor therapy and stroke risk reduction: an analysis of clinical trials data. Atherosclerosis. 1998 May;138(1):11–24.
  • Pedersen TR, Olsson AG, Faergeman O, et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). 1998. Atheroscler Suppl. 2004 Oct;5(3):99–106.
  • Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and recurrent events trial investigators. N Engl J Med. 1996 Oct 3;335(14):1001–1009.
  • The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998 Nov 5;339(19):1349–1357.
  • West of Scotland Coronary Prevention Study Group. Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation. 1998 Apr 21;97(15):1440–1445.
  • Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Drugs. 2004;64(Suppl 2):43–60.
  • Amarenco P, Lavallee P, Touboul PJ. Stroke prevention, blood cholesterol, and statins. Lancet Neurol. 2004 May;3(5):271–278.
  • Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ (Clinical Research Ed). 2003 Jun 28;326(7404):1423.
  • Russell RG. Bisphosphonates: the first 40 years. Bone. 2011 Jul;49(1):2–19.
  • Hata T, Soga J, Hidaka T, et al. Calcium channel blocker and Rho-associated kinase activity in patients with hypertension. J Hypertens. 2011 Feb;29(2):373–379.
  • Zee RYL, Wang QM, Chasman DI, et al. Gene variations of ROCKs and risk of ischaemic stroke: the Women’s Genome Health Study. Clin Sci. 2014 Jun;126(12):829–835.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.