RETRACTED: Inhibition of Rho‐kinase by Fasudil protects dopamine neurons and attenuates inflammatory response in an intranasal lipopolysaccharide‐mediated Parkinson's model
Abstract
Microglia activation and inflammatory factors in brain microenvironment are associated with degeneration of neurons in the substantia nigra ( SN ) of Parkinson's disease ( PD ) patients and various PD models. There is increasing evidence that the Rho/ ROCK (Rho kinase) signalling pathway may play a critical role in the inflammatory response, and ROCK inhibitor has been reported to have neuroprotective effects. In this study, we examined the neuroprotective potential and possible mechanism of ROCK inhibitor Fasudil in an intranasal lipopolysaccharide ( LPS )‐induced PD model. ROCK was activated with LPS stimulation and inhibited by Fasudil treatment in this PD model. Behavioural tests demonstrated a clear improvement in motor performance after Fasudil treatment. Furthermore, Fasudil resulted in a significant attenuation of dopamine cell loss, α‐synuclein accumulation and inflammatory response with the reversion of inflammatory M1 to anti‐inflammatory M2 microglia, decreased NF ‐кB activation, and IL ‐12 and TNF ‐α generation in the SN and olfactory bulb in this model. This study establishes a role for Fasudil in protecting against LPS ‐mediated dopamine degeneration and provides a therapeutic strategy for the treatment of PD .
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ROCK inhibition shifts microglia from their proinflammatory M1 phenotype toward the anti-inflammatory M2 phenotype by inhibiting NF-κB activity and expression of proinflammatory cytokines IL-1β, IL-6, and TNFα, while increasing expression of the anti-inflammatory cytokine IL-10.
“Interestingly, ROCK inhibition has been reported to shift microglia from their proinflammatory M1 phenotype toward the anti-inflammatory M2 phenotype by inhibiting NF-кB activity and expression of the proinflammatory cytokines IL-1β, IL-6, and TNFα, while increasing the expression of the anti-inflammatory cytokine IL-10 [155,156,157].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [157]
Cites
Zhang, W., Wang, T., Pei, Z., Miller, D. S., Wu, X., Block, M. L., Wilson, B., Zhang, W., Zhou, Y., Hong, J.-S., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-2751com · Cited by 1,265 · see citing works
The lipopolysaccharide Parkinson’s disease animal model: mechanistic studies and drug discovery
Dutta, G., Zhang, P., & Liu, B. (2008) · Fundamental & Clinical Pharmacology · doi:10.1111/j.1472-8206.2008.00616.x · Cited by 235 · cited 2× · see citing works
“, 1993), and has been used for the induction of dopamine neurodegeneration through intracranial and intraperitoneal injection (Dutta et al., 2008).”
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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
- He, Q., Li, Y., Guo, S., Wang, Y., Lin, W., Zhang, Q., Wang, J., Ma, C., & Xiao, B.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Department of Neurology Institute of Brain Science Medical School Shanxi Datong University Datong China
- Shanxi University of Traditional Chinese Medicine (CN)
- Corresponding author
- Ma, Cun‐gen
- Xiao, Bao‐Guo
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2015-12-28
- Volume
- 43
- Issue
- 1
- Pages
- 41-52
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2212511534
- Cited by
- 48
- References
- 2
- Citations by year
- 2025: 5 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 7 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 2
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- retraction (2024-11-12)
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Foundation of Natural Science of China (81070956, 81371414, 81272163, 81501085)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, fasudil, Rho kinase inhibition, dopaminergic neurons, substantia nigra, microglial polarization, neuroinflammation, alpha-synuclein, NF-κB, IL-12, TNF-α, motor function, olfactory bulb
- MeSH terms
- Administration, Intranasal, Animals, Encephalitis, Female, Lipopolysaccharides, Mice, Inbred C57BL, Motor Activity, Olfactory Bulb, Substantia Nigra, Signal Transduction, NF-kappa B, Microglia, Neuroprotective Agents, Inflammation Mediators, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Parkinsonian Disorders, alpha-Synuclein, rho-Associated Kinases, Dopaminergic Neurons
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