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Cited by 349Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsInflammasome and immune disorders

The DOI matches its Crossref record; 172 of the 173 references it cites were found in a registry or an index, and 1 are not checked yet.

Microglia receptors and their implications in the response to amyloid β for Alzheimer’s disease pathogenesis

Open access
Doens, Deborah, Fernández, Patricia L·2014·Journal of Neuroinflammation
DOI 10.1186/1742-2094-11-48PMC PMC3975152
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Abstract

Alzheimer's disease (AD) is a major public health problem with substantial economic and social impacts around the world. The hallmarks of AD pathogenesis include deposition of amyloid β (Aβ), neurofibrillary tangles, and neuroinflammation. For many years, research has been focused on Aβ accumulation in senile plaques, as these aggregations were perceived as the main cause of the neurodegeneration found in AD. However, increasing evidence suggests that inflammation also plays a critical role in the pathogenesis of AD. Microglia cells are the resident macrophages of the brain and act as the first line of defense in the central nervous system. In AD, microglia play a dual role in disease progression, being essential for clearing Aβ deposits and releasing cytotoxic mediators. Aβ activates microglia through a variety of innate immune receptors expressed on these cells. The mechanisms through which amyloid deposits provoke an inflammatory response are not fully understood, but it is believed that these receptors cooperate in the recognition, internalization, and clearance of Aβ and in cell activation. In this review, we discuss the role of several receptors expressed on microglia in Aβ recognition, uptake, and signaling, and their implications for AD pathogenesis.

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Crossref · 10.1186/1742-2094-11-48

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Figure 1 Microglia receptors involved in the amyloid cascade. A variety of microglia receptors are involved in Aβ clearance and in triggering an inflammatory response. Some receptors (RAGE, NLRP3) are mainly implicated in the generation of an inflammatory response by triggering a signaling cascade that results in the production of proinflammatory mediators. Other receptors (SR-AI, TREM2) are involved in the clearance of Aβ by inducing internalization of Aβ fibrils. Some receptors (complement receptors, Fc receptors, FPRL1/FPR2, CD36, TLRs) are involved in both processes. CD33 seems to promote Aβ accumulation.
Figure 1 Microglia receptors involved in the amyloid cascade. A variety of microglia receptors are involved in Aβ clearance and in triggering an inflammatory response. Some receptors (RAGE, NLRP3) are mainly implicated in the generation of an inflammatory response by triggering a signaling cascade that results in the production of proinflammatory mediators. Other receptors (SR-AI, TREM2) are involved in the clearance of Aβ by inducing internalization of Aβ fibrils. Some receptors (complement receptors, Fc receptors, FPRL1/FPR2, CD36, TLRs) are involved in both processes. CD33 seems to promote Aβ accumulation.CC BY · PubMed Central
Figure 2 Cooperation among microglia receptors in Aβ recognition, uptake and signaling. (a) Aβ fibrils are recognized by the complex CD36-α6β1-CD47, generating ROS production. The interaction between CD36 and Aβ provides signals for the assembly of the heterodimer TLR4-TLR6 complex. (b) CD36-TLR4-TLR6 complex activation constitutes the first signal for the transcription of Nlrp3 and il1b. (c) CD36 mediates the internalization of Aβ into the lysosomal compartment. Lysosomal disruption constitutes the second signal for the NLRP3 assembly and the subsequent cleavage of pro-IL-1β, rendering the mature IL-1β. (d) The activation of TLR4 also induces the overexpression of SR-AI, which contributes to the clearance of Aβ.
Figure 2 Cooperation among microglia receptors in Aβ recognition, uptake and signaling. (a) Aβ fibrils are recognized by the complex CD36-α6β1-CD47, generating ROS production. The interaction between CD36 and Aβ provides signals for the assembly of the heterodimer TLR4-TLR6 complex. (b) CD36-TLR4-TLR6 complex activation constitutes the first signal for the transcription of Nlrp3 and il1b. (c) CD36 mediates the internalization of Aβ into the lysosomal compartment. Lysosomal disruption constitutes the second signal for the NLRP3 assembly and the subsequent cleavage of pro-IL-1β, rendering the mature IL-1β. (d) The activation of TLR4 also induces the overexpression of SR-AI, which contributes to the clearance of Aβ.CC BY · PubMed Central

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  1. 10.1146/annurev.bi.63.070194.003125 · DOI

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Metadata

Authors
Doens, D., & Fernández, P. L.
Affiliations
  • Acharya Nagarjuna University (IN)
  • Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (PA)
Corresponding author
Fernández, Patricia L
ORCID
Fernández, Patricia L
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2014
Volume
11
Issue
1
Pages
48
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/1742-2094-11-48
PMC
PMC3975152
OpenAlex
W2100011299
Cited by
348
References
172
Citations by year
2026: 22 · 2025: 42 · 2024: 33 · 2023: 33 · 2022: 36 · 2021: 27 · 2020: 24 · 2019: 24 · 2018: 27 · 2017: 26 · 2016: 24 · 2015: 25 · 2014: 5
FWCI
2.16
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Greater South Information System
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
Alzheimer's disease, amyloid-beta, microglia, innate immune receptors, neuroinflammation, amyloid clearance, receptor signaling, microglial activation, amyloid plaques, neurodegeneration
MeSH terms
Alzheimer Disease, Animals, Humans, Receptors, Immunologic, Amyloid beta-Peptides, Microglia

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