Fasudil, a rho kinase inhibitor, limits motor neuron loss in experimental models of amyotrophic lateral sclerosis
Open accessAbstract
Background and Purpose: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with no effective treatment. Fasudil hydrochloride (fasudil), a potent rho kinase (ROCK) inhibitor, is useful for the treatment of ischaemic diseases. In previous reports, fasudil improved pathology in mouse models of A lzheimer's disease and spinal muscular atrophy, but there is no evidence in that it can affect ALS. We therefore investigated its effects on experimental models of ALS. Experimental Approach: In mice motor neuron (NSC34) cells, the neuroprotective effect of hydroxyfasudil (M3), an active metabolite of fasudil, and its mechanism were evaluated. Moreover, the effects of fasudil, 30 and 100 mg·kg−1, administered via drinking water to mutant superoxide dismutase 1 (SOD1 G93A) mice were tested by measuring motor performance, survival time and histological changes, and its mechanism investigated. Key Results: M3 prevented motor neuron cell death induced by SOD1 G93A. Furthermore, M3 suppressed both the increase in ROCK activity and phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN), and the reduction in phosphorylated Akt induced by SOD1 G93A. These effects of M3 were attenuated by treatment with a PI3K inhibitor (LY294002). Moreover, fasudil slowed disease progression, increased survival time and reduced motor neuron loss, in SOD1 G93A mice. Fasudil also attenuated the increase in ROCK activity and PTEN, and the reduction in A kt in SOD1 G93A mice. Conclusions and Implications: These findings indicate that fasudil may be effective at suppressing motor neuron degeneration and symptom progression in ALS. Hence, fasudil may have potential as a therapeutic agent for ALS treatment.
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.
Integrity signals
Registry
Cites
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.
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 reduces ROCK-mediated activation of PTEN in SOD1G93A mice.
“ROCK inhibition also slowed disease progression and reduced motor neuron loss in SOD1G93A mice through reduced ROCK-mediated activation of PTEN and restored activation of the prosurvival kinase Akt [211].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [211]
ROCK inhibition slows disease progression in SOD1G93A mice.
“ROCK inhibition also slowed disease progression and reduced motor neuron loss in SOD1G93A mice through reduced ROCK-mediated activation of PTEN and restored activation of the prosurvival kinase Akt [211].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [211]
ROCK inhibition restores activation of the prosurvival kinase Akt in SOD1G93A mice.
“ROCK inhibition also slowed disease progression and reduced motor neuron loss in SOD1G93A mice through reduced ROCK-mediated activation of PTEN and restored activation of the prosurvival kinase Akt [211].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [211]
ROCK inhibition reduces motor neuron loss in SOD1G93A mice.
“ROCK inhibition also slowed disease progression and reduced motor neuron loss in SOD1G93A mice through reduced ROCK-mediated activation of PTEN and restored activation of the prosurvival kinase Akt [211].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [211]
Activation of the RhoA/ROCK pathway has been implicated in the pathogenesis of ALS, although studied to a lesser degree and focusing on the disease-modifying effects of ROCK inhibition.
“Activation of the RhoA/ROCK pathway has also been implicated in the pathogenesis of ALS, although studied to a lesser degree and focusing on the disease-modifying effects of ROCK inhibition.”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [211]
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
No references could be resolved yet.
Research works printed but not linked: 1
- Jackson M, Ganel R, Rothstein JD (2002). Models of amyotrophic lateral sclerosis. Curr Protoc Neurosci, Chapter 9, Unit 9.
Cited by
Sorted by citations
Drug repurposing: progress, challenges and recommendations
Pushpakom, S., Iorio, F., Eyers, P. A., Escott, K. J., Hopper, S., Wells, A., Doig, A., Guilliams, T., Latimer, J., McNamee, C., et al. (2019) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.168 · Cited by 4,718 · see citing works
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · see citing works
RhoA Signaling in Neurodegenerative Diseases
Schmidt, S. I., Blaabjerg, M., Freude, K., & Meyer, M. (2022) · Cells · doi:10.3390/cells11091520 · Cited by 110 · see citing works
- Authors
- Takata, M., Tanaka, H., Kimura, M., Nagahara, Y., Tanaka, K., Kawasaki, K., Seto, M., Tsuruma, K., Shimazawa, M., & Hara, H.
- Affiliations
- Gifu Pharmaceutical University (JP)
- Asahi Kasei Therapeutics Corporation (Japan) (JP)
- Corresponding author
- Hara, H
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2013-08-27
- Volume
- 170
- Issue
- 2
- Pages
- 341-351
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC3834758
- OpenAlex
- W1498274359
- Cited by
- 131
- References
- 0
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 13 · 2023: 5 · 2022: 8 · 2021: 14 · 2020: 16 · 2019: 8 · 2018: 11 · 2017: 10 · 2016: 4 · 2015: 13 · 2014: 9 · 2013: 2
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- fasudil, ROCK inhibitor, amyotrophic lateral sclerosis, motor neuron degeneration, hydroxyfasudil, SOD1 G93A mice, PTEN, Akt signaling, phosphatidylinositol 3-kinase, neuroprotection
- MeSH terms
- Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Male, Mice, Transgenic, Motor Neurons, Phosphorylation, Superoxide Dismutase, Survival Rate, Disease Progression, Neuroprotective Agents, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Phosphatidylinositol 3-Kinases, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, 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
