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Cited by 55MicroRNA in disease regulationProtein Kinase Regulation and GTPase SignalingNeuroinflammation and Neurodegeneration Mechanisms

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

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Kimura, Tetsu, Horikoshi, Yuta, Kuriyagawa, Chika, Niiyama, Yukitoshi·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms222111573PMC PMC8584200
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Abstract

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.

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  • Dysregulation of Rho GTPases has been studied in relation to cancer progression, but accumulating evidence supports a role in traumatic brain injury and neurodegenerative diseases.

    “Dysregulation of Rho GTPases has been studied in relation to cancer progression for a number of years [3], but accumulating evidence supports a role in traumatic brain injury and neurodegenerative diseases as well [4,5,6,7].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [6]

    The Introduction links excessive Rho/ROCK activity to Parkinson’s and Alzheimer’s diseases, supporting the neurodegenerative-disease part of the claim. The paper discusses ischemic stroke and spinal cord injury, but the passages found do not address traumatic brain injury. The cancer clause is cited to a different source [3], so it is not part of this verdict. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Emerging evidence points toward a role of aberrant RhoA signaling in neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis.

    “Indeed, emerging evidence points toward a role of aberrant RhoA signaling in neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis.”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [6]

    The Introduction (page not provided) says excessive Rho/ROCK activity contributes to Parkinson’s and Alzheimer’s diseases. The cited passages do not extend that statement to Huntington’s disease or amyotrophic lateral sclerosis, so the full list is not supported. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Kimura, T., Horikoshi, Y., Kuriyagawa, C., & Niiyama, Y.
Affiliations
Akita University (JP)
Corresponding author
Kimura, Tetsu
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-10-26
Volume
22
Issue
21
Pages
11573
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms222111573
PMC
PMC8584200
OpenAlex
W3208500115
Cited by
55
References
6
Citations by year
2026: 7 · 2025: 14 · 2024: 8 · 2023: 14 · 2022: 12
FWCI
1.03
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (acceptedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
RhoA/ROCK signaling, non-coding RNA, ischemic stroke, spinal cord injury, microRNA, long non-coding RNA, neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrocyte activation, axon growth inhibition, ROCK inhibitor, fasudil, oxidative stress
MeSH terms
Ischemic Stroke, Animals, Brain Ischemia, Humans, Spinal Cord, Spinal Cord Injuries, Signal Transduction, RNA, Untranslated, rho-Associated Kinases

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