Involvement of microglial RhoA/Rho-kinase pathway activation in the dopaminergic neuron death. Role of angiotensin via angiotensin type 1 receptors
Open accessAbstract
It has recently been shown that the dopaminergic cell loss induced by neurotoxins is enhanced by brain angiotensin II (AII) via type 1 receptors (AT1). However, the mechanisms involved in the dopaminergic degeneration and the brain inflammatory effects of AII have not been clarified. The RhoA-Rho-Kinase (ROCK) pathway may play a critical role in the inflammatory and oxidative effects of AII. In the substantia nigra of mice, administration of the dopaminergic neurotoxin MPTP induced an increase in the expression of RhoA and ROCK II mRNA levels and ROCK activity, which were inhibited by AT1 receptor deletion (i.e., in AT1a null mice treated with MPTP). Administration of the ROCK inhibitor Y-27632 or AT1 deletion induced a significant decrease in MPTP-induced microglial activation and dopaminergic cell death. In rat primary mesencephalic cultures treated with MPP(+), the increase in dopaminergic cell loss induced by AII administration was also inhibited by treatment with Y27632. Intense expression of ROCK II was observed in the microglial cells in the substantia nigra of mice treated with MPTP, and the major role of the microglial ROCK was confirmed by comparing mesencephalic cultures with and without microglia. Activation of the RhoA/ROCK pathway is involved in the MPTP-induced dopaminergic degeneration, and in the enhancing effect of AII/AT1 activation on the microglial response and dopaminergic degeneration. ROCK inhibitors and AT1 receptor antagonists may provide new neuropr…
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The neuroprotective effect of ROCK inhibition in MPTP models is attributed to inhibition of the MPTP-induced microglial inflammatory response and to a direct protective effect on the dopaminergic neuritic network in vitro and the striatal axonal innervation in vivo.
“The neuroprotective effect was attributed to inhibition of the MPTP-induced microglial inflammatory response [171,173,174] and to a direct protective effect on the dopaminergic neuritic network in vitro and the striatal axonal innervation in vivo [172,174].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [173]
The role of RhoA signaling in PD pathogenesis is supported by studies of mice treated with the dopaminergic neurotoxin MPTP that show an upregulation of RhoA and ROCK in the substantia nigra pars compacta.
“The role of RhoA signaling in PD pathogenesis is supported by studies of mice treated with the dopaminergic neurotoxin MPTP that show an upregulation of RhoA and ROCK in the substantia nigra pars compacta [173].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [173]
ROCK inhibition protects against MPTP-induced dopaminergic cell death in both mice and primary cultures of dopaminergic neurons.
“ROCK inhibition was found to protect against the MPTP-induced dopaminergic cell death in both mice and primary cultures of dopaminergic neurons [172,173].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [173]
Cites
Doughan, A. K., Harrison, D. G., & Dikalov, S. I. (2008) · Circulation Research · doi:10.1161/circresaha.107.162800 · Cited by 710 · see citing works
Babior, B. M. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2003.12.001 · Cited by 705 · see citing works
Glial reactions in Parkinson's disease
McGeer, P. L., & McGeer, E. G. (2008) · Movement Disorders · doi:10.1002/mds.21751 · Cited by 701 · see citing works
The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases
Cai, H., Griendling, K. K., & Harrison, D. G. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00233-5 · Cited by 687 · see citing works
Vulnerability of mesostriatal dopaminergic neurons in Parkinson’s disease
González-Hernández, T. (2010) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2010.00140 · Cited by 65 · see citing works
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Daniele, S. G., Béraud, D., Davenport, C., Cheng, K., Yin, H., & Maguire-Zeiss, K. A. (2015) · Science Signaling · doi:10.1126/scisignal.2005965 · Cited by 303 · 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
- Villar-Cheda, B., Dominguez-Meijide, A., Joglar, B., Rodriguez-Perez, A. I., Guerra, M. J., & Labandeira-Garcia, J. L.
- Affiliations
- Universidade de Santiago de Compostela (ES)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 47
- Issue
- 2
- Pages
- 268-279
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2076429912
- Cited by
- 104
- References
- 5
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 10 · 2015: 14 · 2014: 12 · 2013: 11 · 2012: 2
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministerio de Sanidad, Consumo y Bienestar Social
- Ministerio de Ciencia e Innovación
- Universidade de Santiago de Compostela
- 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
- RhoA/ROCK signaling, microglial activation, dopaminergic neuron death, angiotensin II, angiotensin II type 1 receptor, MPTP, MPP+, substantia nigra, Parkinson's disease, neuroinflammation, ROCK inhibitor, neuroprotection, oxidative stress
- MeSH terms
- Amides, Angiotensins, Animals, Cells, Cultured, Enzyme Inhibitors, Male, Mice, Inbred C57BL, Parkinson Disease, Pyridines, Signal Transduction, Cell Death, Microglia, Mice, Knockout, rho GTP-Binding Proteins, rhoA GTP-Binding Protein, Receptor, Angiotensin, Type 1, Mice, rho-Associated Kinases, Dopaminergic Neurons
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