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Cited by 35Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

The adhesion and migration of microglia to β-amyloid (Aβ) is decreased with aging and inhibited by Nogo/NgR pathway

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Fang, Yinquan, Wang, Jianing, Yao, Lemeng, Li, Chenhui, Wang, Jing, Liu, Yuan, Tao, Xia, Sun, Hao +1 more·2018·Journal of Neuroinflammation
DOI 10.1186/s12974-018-1250-1PMC PMC6054753
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Abstract

Alzheimer’s disease is characterized by progressive accumulation of β-amyloid (Aβ)-containing amyloid plaques, and microglia play a critical role in internalization and degradation of Aβ. Our previous research confirmed that Nogo-66 binding to Nogo receptors (NgR) expressed on microglia inhibits cell adhesion and migration in vitro. The adhesion and migration of microglia isolated from WT and APP/PS1 mice from different ages were measured by adhesion assays and transwells. After NEP1-40 (a competitive antagonist of Nogo/NgR pathway) was intracerebroventricularly administered via mini-osmotic pumps for 2 months in APP/PS1 transgenic mice, microglial recruitment toward Aβ deposits and CD36 expression were determined. In this paper, we found that aging led to a reduction of microglia adhesion and migration to fAβ 1–42 in WT and APP/PS1 mice. The adhesion and migration of microglia to fAβ 1–42 were downregulated by the Nogo, which was mediated by NgR, and the increased inhibitory effects of the Nogo could be observed in aged mice. Moreover, Rho GTPases contributed to the effects of the Nogo on adhesion and migration of microglia to fAβ 1–42 by regulating cytoskeleton arrangement. Furthermore, blocking the Nogo/NgR pathway enhanced recruitment of microglia toward Aβ deposits and expression of CD36 in APP/PS1 mice. Taken together, Nogo/NgR pathway could take part in Aβ pathology in AD by modulating microglial adhesion and migration to Aβ and the Nogo/NgR pathway might be an important target for treating AD.

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Sorted by citations

Authors
Fang, Y., Wang, J., Yao, L., Li, C., Wang, J., Liu, Y., Tao, X., Sun, H., & Liao, H.
Affiliations
China Pharmaceutical University (CN)
Corresponding author
Liao, Hong
ORCID
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2018-07-20
Volume
15
Issue
1
Pages
210-210
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/s12974-018-1250-1
PMC
PMC6054753
OpenAlex
W2883127413
Cited by
35
References
6
Citations by year
2026: 3 · 2025: 5 · 2024: 1 · 2023: 7 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 3
FWCI
1.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81271338, 81772063, 81572240)
  • China Pharmaceutical University
  • Specialized Research Fund for the Doctoral Program of Higher Education of China (20130096110011)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
microglia, amyloid-beta, Nogo-66, Nogo receptor, microglial migration, aging, Alzheimer's disease, APP/PS1 mice, Rho GTPases, cytoskeleton, CD36, NEP1-40, amyloid plaques, microglial recruitment
MeSH terms
Nogo Receptors, Nogo Proteins, Aging, Alzheimer Disease, Animals, Brain, Cell Adhesion, Cell Movement, Disease Models, Animal, Humans, Mice, Inbred C57BL, Mice, Transgenic, Myelin Proteins, Peptide Fragments, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microglia, rhoA GTP-Binding Protein, cdc42 GTP-Binding Protein, rac1 GTP-Binding Protein, Mice, Presenilin-1

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