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Cited by 77Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

Modulation of Microglial Activity by Rho-Kinase (ROCK) Inhibition as Therapeutic Strategy in Parkinson’s Disease and Amyotrophic Lateral Sclerosis

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Roser, Anna-Elisa, Tönges, Lars, Lingor, Paul·2017·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2017.00094PMC PMC5378706
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Abstract

Neurodegenerative diseases are characterized by the progressive degeneration of neurons in the central and peripheral nervous system (CNS, PNS), resulting in a reduced innervation of target structures and a loss of function. A shared characteristic of many neurodegenerative diseases is the infiltration of microglial cells into affected brain regions. During early disease stages microglial cells often display a rather neuroprotective phenotype, but switch to a more pro-inflammatory neurotoxic phenotype in later stages of the disease, contributing to the neurodegeneration. Activation of the Rho kinase (ROCK) pathway appears to be instrumental for the modulation of the microglial phenotype: increased ROCK activity in microglia mediates mechanisms of the inflammatory response and is associated with improved motility, increased production of reactive oxygen species (ROS) and release of inflammatory cytokines. Recently, several studies suggested inhibition of ROCK signaling as a promising treatment option for neurodegenerative diseases. In this review article, we discuss the contribution of microglial activity and phenotype switch to the pathophysiology of Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS), two devastating neurodegenerative diseases without disease-modifying treatment options. Furthermore, we describe how ROCK inhibition can influence the microglial phenotype in disease models and explore ROCK inhibition as a future treatment option for PD and ALS.

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  • The role of RhoA/ROCK signaling in regulating cytoskeletal dynamics is particularly important for the activation of microglial migration and phagocytosis.

    “The role of RhoA/ROCK signaling in regulating cytoskeletal dynamics, as described above, is particularly important for the activation of microglial migration and phagocytosis [154].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [154]

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Cited by

Sorted by citations

Authors
Roser, A.-E., Tönges, L., & Lingor, P.
Affiliations
  • Universitätsmedizin Göttingen (DE)
  • Ruhr University Bochum (DE)
Corresponding author
Lingor, Paul
ORCID
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2017-04-04
Volume
9
Pages
94-94
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2017.00094
PMC
PMC5378706
OpenAlex
W2605257773
Cited by
77
References
4
Citations by year
2026: 7 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 14 · 2021: 10 · 2020: 12 · 2019: 8 · 2018: 6 · 2017: 2
FWCI
0.73
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
  • GRO (submittedVersion, cc-by)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Rho kinase inhibition, microglial activation, Parkinson's disease, amyotrophic lateral sclerosis, neuroinflammation, neurodegeneration, reactive oxygen species, inflammatory cytokines, microglial motility, disease-modifying therapy

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