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Cited by 36Parkinson's Disease Mechanisms and TreatmentsProtein Kinase Regulation and GTPase SignalingCell Adhesion Molecules Research

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The Role of LRRK2 in the Regulation of Monocyte Adhesion to Endothelial Cells

Hongge, Li, Kexin, Guo, Xiaojie, Mou, Nian, Xiong, Jinsha, Huang·2015·Journal of Molecular Neuroscience
DOI 10.1007/s12031-014-0312-9
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Abstract

The leucine-rich repeat kinase 2 (LRRK2) gene was discovered to encode a member of an evolutionarily conserved family of proteins marked by GTPase domains usually in combination with kinase domains. Missense mutations in both the kinase and GTPase domains in LRRK2 have been found to cause late-onset Parkinson's disease (PD). In this study, we investigated the effects of the LRRK2 on endothelial inflammation. We first demonstrated that the LRRK2 is expressed in endothelial cells. We also report here that IL-1β can possibly increase LRRK2 expression in human umbilical vein endothelial cells (HUVECs). Wild-type LRRK2 (LRRK2(wt)) expression induces expression of vascular cell adhesion molecule 1 (VCAM-1) which is further exacerbated in cells expressing PD-associated LRRK2 G2019S mutants (LRRK2(G2019S)). Importantly, induction of VCAM-1 is almost completely blocked in cells expressing the GTP-binding-deficient mutant K1347A of LRRK2 (LRRK2(K1347A)). In addition, overexpression of LRRK2(wt) and LRRK2(G2019S) were found to cause an increase in monocyte attachment to endothelial cells. Mechanistically, we found that LRRK2 increases the transcriptional activity of nuclear factor κB (NF-κB) by increasing phosphorylation levels of IκBα. These findings suggest that inhibition of LRRK2 kinase activity may be a potential target for treatment of endothelial dysfunction.

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Metadata

Authors
Hongge, L., Kexin, G., Xiaojie, M., Nian, X., & Jinsha, H.
Affiliations
Wuhan Union Hospital (CN)
Corresponding author
Hongge, Li
Venue
Journal of Molecular Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2014-05-01
Volume
55
Issue
1
Pages
233-239
ISSN
  • 0895-8696 (ISSN-L)
  • 1559-1166
DOI
10.1007/s12031-014-0312-9
OpenAlex
W2081209272
Cited by
36
References
1
Citations by year
2026: 3 · 2025: 5 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 2 · 2014: 1
FWCI
1.52
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Journal of Molecular Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
LRRK2, monocyte adhesion, endothelial cells, Parkinson's disease, LRRK2 G2019S mutation, VCAM-1, IL-1β, NF-κB, IκBα phosphorylation, endothelial inflammation, endothelial dysfunction, LRRK2 kinase activity
MeSH terms
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Cell Adhesion, Humans, Inflammation, Monocytes, Mutation, NF-kappa B, Protein Serine-Threonine Kinases, Vascular Cell Adhesion Molecule-1, Interleukin-1beta, Human Umbilical Vein Endothelial Cells

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