CoChat
Sign Up
Cited by 40Parkinson's Disease Mechanisms and TreatmentsNeurological disorders and treatmentsNuclear Receptors and Signaling

Rho kinase inhibitor fasudil reduces l‐DOPA‐induced dyskinesia in a rat model of Parkinson's disease

Open access
Lopez‐Lopez, Andrea, Labandeira, Carmen M., Labandeira‐Garcia, Jose L., Muñoz, Ana·2020·British Journal of Pharmacology
DOI 10.1111/bph.15275PMC PMC7707090
Open this paper in CoChat — free account

Abstract

Background and Purpose: Rho kinase (ROCK) activation is involved in neuroinflammatory processes leading to progression of neurodegenerative diseases such as Parkinson's disease. Furthermore, ROCK plays a major role in angiogenesis. Neuroinflammation and angiogenesis are mechanisms involved in developing l‐DOPA‐induced dyskinesias (LID). However, it is not known whether ROCK plays a role in LID and whether ROCK inhibitors may be useful against LID. Experimental Approach: In rats, we performed short‐ and long‐term dopaminergic lesions using 6‐hydroxydopamine and developed a LID model. Effects of dopaminergic lesions and LID on the RhoA/ROCK levels were studied by western blot, real‐time PCR analyses and ROCK activity assays in the substantia nigra and striatum. The effects of the ROCK inhibitor fasudil on LID were particularly investigated. Key Results: Short‐term 6‐hydroxydopamine lesions increased nigrostriatal RhoA/ROCK expression, apparently related to the active neuroinflammatory process. However, long‐term dopaminergic denervation (completed and stabilized lesions) led to a decrease in RhoA/ROCK levels. Rats with LID showed a significant increase of RhoA and ROCK expression. The development of LID was reduced by the ROCK inhibitor fasudil (10 and 40 mg·kg−1), without interfering with the therapeutic effect of l‐DOPA. Interestingly, treatment of 40 mg·kg−1 of fasudil also induced a significant reduction of dyskinesia in rats with previously established LID. Conclusion and Implications: The present results suggest that ROCK is involved in the pathophysiology of LID and that ROCK inhibitors such as fasudil may be a novel target for preventing or treating LID. Furthermore, previous studies have revealed neuroprotective effects of ROCK inhibitors.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/bph.15275

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • ROCK inhibition using Fasudil reduces the development of L-DOPA-induced dyskinesia and inhibits already established dyskinesia affecting the therapeutic effect of L-DOPA.

    “In 6-hydroxydopamine lesioned rats with dyskinesia, RhoA and ROCK were increased in the substantia nigra and striatum, and ROCK inhibition using Fasudil was found to reduce the development of L-DOPA-induced dyskinesia and to inhibit already established dyskinesia affecting the therapeutic effect of L-DOPA [179].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [179]

    The Discussion (section 4) supports the claim that fasudil reduced both the development of dyskinesia and already established dyskinesia. But it explicitly says this occurred without affecting the therapeutic effect of l-DOPA, contrary to the citing sentence’s statement that it affected that effect. The Results (section 3.2) likewise report that the motor benefit of l-DOPA was preserved. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • In 6-hydroxydopamine lesioned rats with dyskinesia, RhoA and ROCK are increased in the substantia nigra and striatum.

    “In 6-hydroxydopamine lesioned rats with dyskinesia, RhoA and ROCK were increased in the substantia nigra and striatum, and ROCK inhibition using Fasudil was found to reduce the development of L-DOPA-induced dyskinesia and to inhibit already established dyskinesia affecting the therapeutic effect of L-DOPA [179].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [179]

  • RhoA/ROCK signaling has very recently been linked to L-DOPA-induced dyskinesia in a rat model of Parkinson's disease.

    “RhoA/ROCK signaling has very recently also been linked to L-DOPA-induced dyskinesia in a rat model of Parkinson’s disease.”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [179]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 61

  1. Alexander, S. P. H. , Christopoulos, A. , Davenport, A. P. , Kelly, E. , Mathie, A. , Peters, J. A. , … Pawson, A. J. (2019). The Concise Guide to PHARMACOLOGY 2019/20: G protein‐coupled receptors. British Journal of Pharmacology, 176(Suppl 1), S21–S141. 10.1111/bph.14748 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  2. Alexander, S. P. H. , Roberts, R. E. , Broughton, B. R. S. , Sobey, C. G. , George, C. H. , Stanford, S. C. , … Ahluwalia, A. (2018). Goals and practicalities of immunoblotting and immunohistochemistry: A guide for submission to the British Journal of Pharmacology . British Journal of Pharmacology, 175, 407–411. 10.1111/bph.14112 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  3. Barcia, C. , Ros, C. M. , Annese, V. , Carrillo‐de Sauvage, M. A. , Ros‐Bernal, F. , Gomez, A. , … Herrero, M. T. (2012). ROCK/Cdc42‐mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo. Scientific Reports, 2, 809 10.1038/srep00809 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  4. Barnum, C. J. , Eskow, K. L. , Dupre, K. , Blandino, P. Jr. , Deak, T. , & Bishop, C. (2008). Exogenous corticosterone reduces l‐DOPA‐induced dyskinesia in the hemi‐parkinsonian rat: Role for interleukin‐1β. Neuroscience, 156, 30–41. 10.1016/j.neuroscience.2008.07.016 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  5. Boi, L. , Pisanu, A. , Greig, N. H. , Scerba, M. T. , Tweedie, D. , Mulas, G. , … Carta, A. R. (2019). Immunomodulatory drugs alleviate l‐dopa‐induced dyskinesia in a rat model of Parkinson's disease. Movement Disorders: Official Journal of the Movement Disorder Society, 34, 1818–1830. 10.1002/mds.27799 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  6. Borrajo, A. , Rodriguez‐Perez, A. I. , Diaz‐Ruiz, C. , Guerra, M. J. , & Labandeira‐Garcia, J. L. (2014). Microglial TNF‐α mediates enhancement of dopaminergic degeneration by brain angiotensin. Glia, 62, 145–157. 10.1002/glia.22595 [DOI] [PubMed] [Google Scholar] · DOI
  7. Borrajo, A. , Rodriguez‐Perez, A. I. , Villar‐Cheda, B. , Guerra, M. J. , & Labandeira‐Garcia, J. L. (2014). Inhibition of the microglial response is essential for the neuroprotective effects of Rho‐kinase inhibitors on MPTP‐induced dopaminergic cell death. Neuropharmacology, 85, 1–8. 10.1016/j.neuropharm.2014.05.021 [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  8. Bortolanza, M. , Cavalcanti‐Kiwiatkoski, R. , Padovan‐Neto, F. E. , da‐Silva, C. A. , Mitkovski, M. , Raisman‐Vozari, R. , & Del‐Bel, E. (2015). Glial activation is associated with l‐DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson's disease. Neurobiology of Disease, 73, 377–387. 10.1016/j.nbd.2014.10.017 [DOI] [PubMed] [Google Scholar] · DOI
  9. Bryan, B. A. , Dennstedt, E. , Mitchell, D. C. , Walshe, T. E. , Noma, K. , Loureiro, R. , … Patricia, D. A. A. (2010). RhoA/ROCK signaling is essential for multiple aspects of VEGF‐mediated angiogenesis. FASEB Journal, 24, 3186–3195. 10.1096/fj.09-145102 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  10. Carbajo‐Lozoya, J. , Lutz, S. , Feng, Y. , Kroll, J. , Hammes, H. P. , & Wieland, T. (2012). Angiotensin II modulates VEGF‐driven angiogenesis by opposing effects of type 1 and type 2 receptor stimulation in the microvascular endothelium. Cellular Signalling, 24, 1261–1269. 10.1016/j.cellsig.2012.02.005 [DOI] [PubMed] [Google Scholar] · DOI
  11. Carta, M. , Lindgren, H. S. , Lundblad, M. , Stancampiano, R. , Fadda, F. , & Cenci, M. A. (2006). Role of striatal l‐DOPA in the production of dyskinesia in 6‐hydroxydopamine lesioned rats. Journal of NeurochemistryMar, 96(6), 1718–1727. 10.1111/j.1471-4159.2006.03696.x [DOI] [PubMed] [Google Scholar] · DOI
  12. Cenci, M. A. , & Crossman, A. R. (2018). Animal models of l‐dopa‐induced dyskinesia in Parkinson's disease. Movement Disorders: Official Journal of the Movement Disorder Society, 33, 889–899. 10.1002/mds.27337 [DOI] [PubMed] [Google Scholar] · DOI
  13. Cenci, M. A. , & Konradi, C. (2010). Maladaptive striatal plasticity in l‐DOPA‐induced dyskinesia. Progress in Brain Research, 183, 209–233. 10.1016/S0079-6123(10)83011-0 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  14. Chen, M. , Liu, A. , Ouyang, Y. , Huang, Y. , Chao, X. , & Pi, R. (2013). Fasudil and its analogs: A new powerful weapon in the long war against central nervous system disorders? Expert Opinion Investigational Drugs, 22, 537–550. 10.1517/13543784.2013.778242 [DOI] [PubMed] [Google Scholar] · DOI
  15. Defert, O. , & Boland, S. (2017). Rho kinase inhibitors: A patent review (2014–2016). Expert Opinion on Therapeutic Patents, 27, 507–515. 10.1080/13543776.2017.1272579 [DOI] [PubMed] [Google Scholar] · DOI
  16. Espay, A. J. , Morgante, F. , Merola, A. , Fasano, A. , Marsili, L. , Fox, S. H. , … Lang, A. E. (2018). Levodopa‐induced dyskinesia in Parkinson disease: Current and evolving concepts. Annals of Neurology, 84, 797–811. 10.1002/ana.25364 [DOI] [PubMed] [Google Scholar] · DOI
  17. Gerhard, A. , Pavese, N. , Hotton, G. , Turkheimer, F. , Es, M. , Hammers, A. , … Brooks, D. J. (2006). In vivo imaging of microglial activation with [11C](R)‐PK11195 PET in idiopathic Parkinson's disease. Neurobiology of Disease, 21, 404–412. 10.1016/j.nbd.2005.08.002 [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  18. Gu, Q. F. , Yu, J. Z. , Wu, H. , Li, Y. H. , Liu, C. Y. , Feng, L. , … Ma, C. G. (2018). Therapeutic effect of Rho kinase inhibitor FSD‐C10 in a mouse model of Alzheimer's disease. Experimental and Therapeutic Medicine, 16, 3929–3938. 10.3892/etm.2018.6701 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  19. Gunther, R. , Balck, A. , Koch, J. C. , Nientiedt, T. , Sereda, M. , Bahr, M. , … Tonges, L. (2017). Rho kinase inhibition with fasudil in the SOD1G93A mouse model of amyotrophic lateral sclerosis—Symptomatic treatment potential after disease onset. Frontiers in Pharmacology, 8, 17 10.3389/fphar.2017.00017 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  20. Heasman, S. J. , & Ridley, A. J. (2010). Multiple roles for RhoA during T cell transendothelial migration. Small GTPases, 1, 174–179. 10.4161/sgtp.1.3.14724 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  21. Hoang, M. V. , Whelan, M. C. , & Senger, D. R. (2004). Rho activity critically and selectively regulates endothelial cell organization during angiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 101, 1874–1879. 10.1073/pnas.0308525100 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  22. Honing, H. , van den Berg, T. K. , van der Pol, S. M. , Dijkstra, C. D. , van der Kammen, R. A. , Collard, J. G. , & de Vries, H. E. (2004). RhoA activation promotes transendothelial migration of monocytes via ROCK. Journal of Leukocyte Biology, 75, 523–528. 10.1189/jlb.0203054 [DOI] [PubMed] [Google Scholar] · DOI
  23. Johnston, T. H. , Lacoste, A. M. B. , Visanji, N. P. , Lang, A. E. , Fox, S. H. , & Brotchie, J. M. (2019). Repurposing drugs to treat l‐DOPA‐induced dyskinesia in Parkinson's disease. Neuropharmacology, 147, 11–27. 10.1016/j.neuropharm.2018.05.035 [DOI] [PubMed] [Google Scholar] · DOI
  24. Kim, J. H. , Lee, H. W. , Hwang, J. , Kim, J. , Lee, M. J. , Han, H. S. , … Suk, K. (2012). Microglia‐inhibiting activity of Parkinson's disease drug amantadine. Neurobiology of Aging, 33, 2145–2159. 10.1016/j.neurobiolaging.2011.08.011 [DOI] [PubMed] [Google Scholar] · DOI
  25. Koch, J. C. , Tatenhorst, L. , Roser, A. E. , Saal, K. A. , Tonges, L. , & Lingor, P. (2018). ROCK inhibition in models of neurodegeneration and its potential for clinical translation. Pharmacology & Therapeutics, 189, 1–21. 10.1016/j.pharmthera.2018.03.008 [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  26. Labandeira‐Garcia, J. L. , Rodriguez‐Perez, A. I. , Villar‐Cheda, B. , Borrajo, A. , Dominguez‐Meijide, A. , & Guerra, M. J. (2015). Rho kinase and dopaminergic degeneration: A promising therapeutic target for Parkinson's disease. The Neuroscientist: A Review Journal Bringing Neurobiology, Neurology and Psychiatry, 21, 616–629. 10.1177/1073858414554954 [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  27. Labandeira‐Garcia, J. L. , Rozas, G. , Lopez‐Martin, E. , Liste, I. , & Guerra, M. J. (1996). Time course of striatal changes induced by 6‐hydroxydopamine lesion of the nigrostriatal pathway, as studied by combined evaluation of rotational behaviour and striatal Fos expression. Experimental Brain Research, 108, 69–84. 10.1007/BF00242905 [DOI] [PubMed] [Google Scholar] · DOI
  28. Lerner, R. P. , Francardo, V. , Fujita, K. , Bimpisidis, Z. , Jourdain, V. A. , Tang, C. C. , … Eidelberg, D. (2017). Levodopa‐induced abnormal involuntary movements correlate with altered permeability of the blood‐brain‐barrier in the basal ganglia. Scientific Reports, 7, 16005 10.1038/s41598-017-16228-1 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  29. Li, M. , Yasumura, D. , Ma, A. A. , Matthes, M. T. , Yang, H. , Nielson, G. , … Diamond, M. I. (2013). Intravitreal administration of HA‐1077, a ROCK inhibitor, improves retinal function in a mouse model of Huntington disease. PLoS ONE, 8, e56026 10.1371/journal.pone.0056026 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  30. Lilley, E. , Stanford, S. C. , Kendall, D. E. , Alexander, S. P. , Cirino, G. , Docherty, J. R. , … Ahluwalia, A. (2020). ARRIVE 2.0 and the British Journal of Pharmacology: Updated guidance for 2020. British Journal of Pharmacology. 10.1111/bph.15178 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  31. Lingor, P. , Weber, M. , Camu, W. , Friede, T. , Hilgers, R. , Leha, A. , … Bidner, H. (2019). ROCK‐ALS: Protocol for a randomized, placebo‐controlled, double‐blind phase IIa trial of safety, tolerability and efficacy of the Rho kinase (ROCK) inhibitor fasudil in amyotrophic lateral sclerosis. Frontiers in Neurology, 10, 293 10.3389/fneur.2019.00293 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  32. Mair, K. M. , MacLean, M. R. , Morecroft, I. , Dempsie, Y. , & Palmer, T. M. (2008). Novel interactions between the 5‐HT transporter, 5‐HT1B receptors and Rho kinase in vivo and in pulmonary fibroblasts. British Journal of Pharmacology, 155, 606–616. 10.1038/bjp.2008.310 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  33. Moskal, N. , Riccio, V. , Bashkurov, M. , Taddese, R. , Datti, A. , Lewis, P. N. , & Angus McQuibban, G. (2020). ROCK inhibitors upregulate the neuroprotective Parkin‐mediated mitophagy pathway. Nature Communications, 11, 88 10.1038/s41467-019-13781-3 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  34. Mulas, G. , Espa, E. , Fenu, S. , Spiga, S. , Cossu, G. , Pillai, E. , … Spolitu, S. (2016). Differential induction of dyskinesia and neuroinflammation by pulsatile versus continuous l‐DOPA delivery in the 6‐OHDA model of Parkinson's disease. Experimental Neurology, 286, 83–92. 10.1016/j.expneurol.2016.09.013 [DOI] [PubMed] [Google Scholar] · DOI
  35. Muñoz, A. , Garrido‐Gil, P. , Dominguez‐Meijide, A. , & Labandeira‐Garcia, J. L. (2014). Angiotensin type 1 receptor blockage reduces l‐dopa‐induced dyskinesia in the 6‐OHDA model of Parkinson's disease. Involvement of vascular endothelial growth factor and interleukin‐1β. Experimental Neurology, 261, 720–732. 10.1016/j.expneurol.2014.08.019 [DOI] [PubMed] [Google Scholar] · DOI
  36. Muñoz, A. , Li, Q. , Gardoni, F. , Marcello, E. , Qin, C. , Carlsson, T. , … Carta, M. (2008). Combined 5‐HT1A and 5‐HT1B receptor agonists for the treatment of l‐DOPA‐induced dyskinesia. Brain, 131, 3380–3394. 10.1093/brain/awn235 [DOI] [PubMed] [Google Scholar] · DOI
  37. Nakabayashi, H. , & Shimizu, K. (2011). HA1077, a Rho kinase inhibitor, suppresses glioma‐induced angiogenesis by targeting the Rho‐ROCK and the mitogen‐activated protein kinase kinase/extracellular signal‐regulated kinase (MEK/ERK) signal pathways. Cancer Science, 102, 393–399. 10.1111/j.1349-7006.2010.01794.x [DOI] [PubMed] [Google Scholar] · DOI
  38. Nohria, A. , Prsic, A. , Liu, P. Y. , Okamoto, R. , Creager, M. A. , Selwyn, A. , & Ganz, P. (2009). Statins inhibit Rho kinase activity in patients with atherosclerosis. Atherosclerosis, 205, 517–521. 10.1016/j.atherosclerosis.2008.12.023 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  39. Ohlin, K. E. , Francardo, V. , Lindgren, H. S. , Sillivan, S. E. , O'Sullivan, S. S. , Luksik, A. S. , … Cenci, M. A. (2011). Vascular endothelial growth factor is upregulated by l‐dopa in the parkinsonian brain: Implications for the development of dyskinesia. Brain, 134, 2339–2357. 10.1093/brain/awr165 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  40. Ohlin, K. E. , Sebastianutto, I. , Adkins, C. E. , Lundblad, C. , Lockman, P. R. , & Cenci, M. A. (2012). Impact of l‐DOPA treatment on regional cerebral blood flow and metabolism in the basal ganglia in a rat model of Parkinson's disease. NeuroImage, 61, 228–239. 10.1016/j.neuroimage.2012.02.066 [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  41. Olsson, M. , Nikkhah, G. , Bentlage, C. , & Bjorklund, A. (1995). Forelimb akinesia in the rat Parkinson model: Differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test. Journal of Neuroscience, 15, 3863–3875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Padovan‐Neto, F. E. , Cavalcanti‐Kiwiatkoviski, R. , Carolino, R. O. , Anselmo‐Franci, J. , & Del Bel, E. (2015). Effects of prolonged neuronal nitric oxide synthase inhibition on the development and expression of l‐DOPA‐induced dyskinesia in 6‐OHDA‐lesioned rats. Neuropharmacology, 89, 87–99. 10.1016/j.neuropharm.2014.08.019 [DOI] [PubMed] [Google Scholar] · DOI
  43. Pisanu, A. , Boi, L. , Mulas, G. , Spiga, S. , Fenu, S. , & Carta, A. R. (2018). Neuroinflammation in l‐DOPA‐induced dyskinesia: Beyond the immune function. Journal of Neural Transmission (Vienna), 125, 1287–1297. 10.1007/s00702-018-1874-4 [DOI] [PubMed] [Google Scholar] · DOI
  44. Rodriguez‐Pallares, J. , Parga, J. A. , Muñoz, A. , Rey, P. , Guerra, M. J. , & Labandeira‐Garcia, J. L. (2007). Mechanism of 6‐hydroxydopamine neurotoxicity: The role of NADPH oxidase and microglial activation in 6‐hydroxydopamine‐induced degeneration of dopaminergic neurons. Journal of Neurochemistry, 103, 145–156. 10.1111/j.1471-4159.2007.04699.x [DOI] [PubMed] [Google Scholar] · DOI
  45. Rodriguez‐Perez, A. I. , Borrajo, A. , Rodriguez‐Pallares, J. , Guerra, M. J. , & Labandeira‐Garcia, J. L. (2015). Interaction between NADPH‐oxidase and Rho‐kinase in angiotensin II‐induced microglial activation. Glia, 63, 466–482. 10.1002/glia.22765 [DOI] [PubMed] [Google Scholar] · DOI
  46. Rodriguez‐Perez, A. I. , Dominguez‐Meijide, A. , Lanciego, J. L. , Guerra, M. J. , & Labandeira‐Garcia, J. L. (2013). Inhibition of Rho kinase mediates the neuroprotective effects of estrogen in the MPTP model of Parkinson's disease. Neurobiology of Disease, 58, 209–219. 10.1016/j.nbd.2013.06.004 [DOI] [PubMed] [Google Scholar] · DOI
  47. Rodriguez‐Perez, A. I. , Valenzuela, R. , Villar‐Cheda, B. , Guerra, M. J. , & Labandeira‐Garcia, J. L. (2012). Dopaminergic neuroprotection of hormonal replacement therapy in young and aged menopausal rats: Role of the brain angiotensin system. Brain, 135, 124–138. 10.1093/brain/awr320 [DOI] [PubMed] [Google Scholar] · DOI
  48. Sakai, N. , Kaufman, S. , & Milstien, S. (1995). Parallel induction of nitric oxide and tetrahydrobiopterin synthesis by cytokines in rat glial cells. Journal of Neurochemistry, 65, 895–902. 10.1046/j.1471-4159.1995.65020895.x [DOI] [PubMed] [Google Scholar] · DOI
  49. Schallert, T. , & Tillerson, J. L. (1999). Intervention strategies for degeneration of dopamine neurons in parkinsonism: Optimising behavioural assessment of outcome. Clifton, NJ: Humana Press. [Google Scholar]
  50. Soto‐Otero, R. , Méndez‐Alvarez, E. , Hermida‐Ameijeiras, A. , Muñoz‐Patiño, A. M. , & Labandeira‐Garcia, J. L. (2000). Autoxidation and neurotoxicity of 6‐hydroxydopamine in the presence of some antioxidants: Potential implication in relation to the pathogenesis of Parkinson's disease. Journal of Neurochemistry, 74, 1605–1612. 10.1046/j.1471-4159.2000.0741605.x [DOI] [PubMed] [Google Scholar] · DOI
  51. Sun, H. , Breslin, J. W. , Zhu, J. , Yuan, S. Y. , & Wu, M. H. (2006). Rho and ROCK signaling in VEGF‐induced microvascular endothelial hyperpermeability. Microcirculation, 13, 237–247. 10.1080/10739680600556944 [DOI] [PubMed] [Google Scholar] · DOI
  52. Suzuki, Y. , Shibuya, M. , Satoh, S. , Sugimoto, Y. , & Takakura, K. (2007). A postmarketing surveillance study of fasudil treatment after aneurysmal subarachnoid hemorrhage. Surgical Neurology, 68, 126–131discussion 131–122. 10.1016/j.surneu.2006.10.037 [DOI] [PubMed] [Google Scholar] · DOI
  53. Takeuchi, H. , Jin, S. , Wang, J. , Zhang, G. , Kawanokuchi, J. , Kuno, R. , … Suzumura, A. (2006). Tumor necrosis factor‐α induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. The Journal of Biological Chemistry, 281, 21362–21368. 10.1074/jbc.M600504200 [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  54. Tatenhorst, L. , Tönges, L. , Saal, K. A. , Koch, J. C. , Szegő, É. M. , Bähr, M. , & Lingor, P. (2014). Rho kinase inhibition by fasudil in the striatal 6‐hydroxydopamine lesion mouse model of Parkinson disease. Journal of Neuropathology and Experimental Neurology, 73, 770–779. 10.1097/NEN.0000000000000095 [DOI] [PubMed] [Google Scholar] · DOI
  55. Teema, A. M. , Zaitone, S. A. , & Moustafa, Y. M. (2016). Ibuprofen or piroxicam protects nigral neurons and delays the development of l‐dopa induced dyskinesia in rats with experimental Parkinsonism: Influence on angiogenesis. Neuropharmacology, 107, 432–450. 10.1016/j.neuropharm.2016.03.034 [DOI] [PubMed] [Google Scholar] · DOI
  56. Villar‐Cheda, B. , Dominguez‐Meijide, A. , Joglar, B. , Rodriguez‐Perez, A. I. , Guerra, M. J. , & Labandeira‐Garcia, J. L. (2012). Involvement of microglial RhoA/Rho‐kinase pathway activation in the dopaminergic neuron death. Role of angiotensin via angiotensin type 1 receptors. Neurobiology of Disease, 47, 268–279. 10.1016/j.nbd.2012.04.010 [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  57. Walsh, S. , Finn, D. P. , & Dowd, E. (2011). Time‐course of nigrostriatal neurodegeneration and neuroinflammation in the 6‐hydroxydopamine‐induced axonal and terminal lesion models of Parkinson's disease in the rat. Neuroscience, 175, 251–261. 10.1016/j.neuroscience.2010.12.005 [DOI] [PubMed] [Google Scholar] · DOI
  58. Wang, T. , Cao, X. , Zhang, T. , Shi, Q. , Chen, Z. , & Tang, B. (2015). Effect of simvastatin on l‐DOPA‐induced abnormal involuntary movements of hemiparkinsonian rats. Neurological Sciences, 36, 1397–1402. 10.1007/s10072-015-2127-z [DOI] [PubMed] [Google Scholar] · DOI
  59. Winkler, C. , Kirik, D. , Bjorklund, A. , & Cenci, M. A. (2002). l‐DOPA‐induced dyskinesia in the intrastriatal 6‐hydroxydopamine model of Parkinson's disease: Relation to motor and cellular parameters of nigrostriatal function. Neurobiology of Disease, 10, 165–186. 10.1006/nbdi.2002.0499 [DOI] [PubMed] [Google Scholar] · DOI
  60. Wu, J. , Li, J. , Hu, H. , Liu, P. , Fang, Y. , & Wu, D. (2012). Rho‐kinase inhibitor, fasudil, prevents neuronal apoptosis via the Akt activation and PTEN inactivation in the ischemic penumbra of rat brain. Cellular and Molecular Neurobiology, 32, 1187–1197. 10.1007/s10571-012-9845-z [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  61. Zhang, S. , Gao, J. , Huang, Y. , & Xu, W. (2009). Study on the pharmacokinetics of fasudil, a selective Rho kinase inhibitor. Asian Journal of Pharmacodynamics and Pharmacokinetics, 9(3), 221–226. [Google Scholar]

Cited by

Sorted by citations

Authors
Lopez‐Lopez, A., Labandeira, C. M., Labandeira‐Garcia, J. L., & Muñoz, A.
Affiliations
  • Laboratory of Cellular and Molecular Neurobiology of Parkinson's Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), Department of Morphological Sciences, IDIS University of Santiago de Compostela Santiago de Compostela Spain
  • Universidade de Santiago de Compostela (ES)
Corresponding author
Muñoz, Ana
ORCID
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2020-11-03
Volume
177
Issue
24
Pages
5622-5641
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
DOI
10.1111/bph.15275
PMC
PMC7707090
OpenAlex
W3090683200
Cited by
40
References
3
Citations by year
2026: 4 · 2025: 6 · 2024: 9 · 2023: 9 · 2022: 7 · 2021: 5
FWCI
2.24
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • British Journal of Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Hispana (submittedVersion)
Funders
  • Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (ED431G/05, ED431C 2018/10)
  • European Regional Development Fund
  • Instituto de Salud Carlos III (RD16/0011/0016)
  • Secretaría de Estado de Investigación, Desarrollo e Innovación (RTI2018‐098830‐B‐I00)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Rho kinase, fasudil, levodopa-induced dyskinesia, Parkinson's disease, RhoA, neuroinflammation, dopaminergic denervation, 6-hydroxydopamine, nigrostriatal pathway, substantia nigra, striatum, angiogenesis, neuroprotection
MeSH terms
Animals, Disease Models, Animal, Dyskinesia, Drug-Induced, Levodopa, Parkinson Disease, Oxidopamine, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Rats, rho-Associated Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review