Rho Kinase and Dopaminergic Degeneration: A Promising Therapeutic Target for Parkinson’s Disease
Abstract
The small GTP-binding protein Rho plays an important role in several cellular functions. RhoA, which is a member of the Rho family, initiates cellular processes that act on its direct downstream effector Rho-associated kinase (ROCK). ROCK inhibition protects against dopaminergic cell death induced by dopaminergic neurotoxins. It has been suggested that ROCK inhibition activates neuroprotective survival cascades in dopaminergic neurons. Axon-stabilizing effects in damaged neurons may represent another mechanism of neuroprotection of dopaminergic neurons by ROCK inhibition. However, it has been shown that microglial cells play a crucial role in neuroprotection by ROCK inhibition and that activation of microglial ROCK mediates major components of the microglial inflammatory response. Additional mechanisms such as interaction with autophagy may also contribute to the neuroprotective effects of ROCK inhibition. Interestingly, ROCK interacts with several brain factors that play a major role in dopaminergic neuron vulnerability such as NADPH-oxidase, angiotensin, and estrogen. ROCK inhibition may provide a new neuroprotective strategy for Parkinson’s disease. This is of particular interest because ROCK inhibitors are currently used against vascular diseases in clinical practice. However, it is necessary to develop more potent and selective ROCK inhibitors to reduce side effects and enhance the efficacy.
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In astrocytes, RhoA/ROCK signaling plays a major role in determining astrocyte morphology and reactive state.
“In astrocytes, RhoA/ROCK signaling plays a major role in determining astrocyte morphology and reactive state [118,160,161], and ROCK inhibition reduces reactive gliosis and increases astrocytic expression of prosurvival genes [162,163].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [160]
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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
- Labandeira-Garcia, J. L., Rodríguez-Perez, A. I., Villar-Cheda, B., Borrajo, A., Dominguez-Meijide, A., & Guerra, M. J.
- Affiliations
- Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
- Universidade de Santiago de Compostela (ES)
- ORCID
- Borrajo, Ana
- Venue
- The Neuroscientist
- Publisher
- SAGE Publications
- Published
- 2014-10-16
- Volume
- 21
- Issue
- 6
- Pages
- 616-629
- ISSN
- 1073-8584 (ISSN-L)
- 1089-4098
- OpenAlex
- W2095788394
- Cited by
- 54
- References
- 7
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 2 · 2021: 7 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 6 · 2015: 6
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Neuroscientist (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Rho kinase, RhoA, dopaminergic neuron loss, Parkinson's disease, neuroprotection, ROCK inhibitor, microglial inflammation, autophagy, NADPH oxidase, angiotensin, estrogen, dopaminergic neurotoxin
- MeSH terms
- Animals, Antiparkinson Agents, Humans, Nerve Degeneration, Parkinson Disease, Neuroprotective Agents, rho-Associated Kinases, Dopaminergic Neurons
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