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Cited by 283Neuroinflammation and Neurodegeneration MechanismsImmune Response and InflammationInflammasome and immune disorders

Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

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Li, Lun, Acioglu, Cigdem, Heary, Robert F., Elkabes, Stella·2021·Brain, Behavior, and Immunity
DOI 10.1016/j.bbi.2020.10.007PMC PMC7543714
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Abstract

Central nervous system (CNS) innate immunity plays essential roles in infections, neurodegenerative diseases, and brain or spinal cord injuries. Astrocytes and microglia are the principal cells that mediate innate immunity in the CNS. Pattern recognition receptors (PRRs), expressed by astrocytes and microglia, sense pathogen-derived or endogenous ligands released by damaged cells and initiate the innate immune response. Toll-like receptors (TLRs) are a well-characterized family of PRRs. The contribution of microglial TLR signaling to CNS pathology has been extensively investigated. Even though astrocytes assume a wide variety of key functions, information about the role of astroglial TLRs in CNS disease and injuries is limited. Because astrocytes display heterogeneity and exhibit phenotypic plasticity depending on the effectors present in the local milieu, they can exert both detrimental and beneficial effects. TLRs are modulators of these paradoxical astroglial properties. The goal of the current review is to highlight the essential roles played by astroglial TLRs in CNS infections, injuries and diseases. We discuss the contribution of astroglial TLRs to host defense as well as the dissemination of viral and bacterial infections in the CNS. We examine the link between astroglial TLRs and the pathogenesis of neurodegenerative diseases and present evidence showing the pivotal influence of astroglial TLR signaling on sterile inflammation in CNS injury. Finally, we define the research questions and areas that warrant further investigations in the context of astrocytes, TLRs, and CNS dysfunction.

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  • α-synuclein can activate glial cells by binding to TLR2 and enhance the spreading of α-synuclein.

    “α-synuclein can also activate glial cells by binding to TLR261,294,295 and enhance the spreading of α-synuclein.70,296”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [295]

    The Parkinson’s disease section identifies aggregated α-synuclein as a TLR2 ligand and reports that α-synuclein activates astroglial TLR2 signaling. It also describes TLR2-mediated transfer from neurons into astrocytes, but does not establish that this interaction enhances the spreading of α-synuclein. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Li, L., Acioglu, C., Heary, R. F., & Elkabes, S.
Affiliations
  • Rutgers, The State University of New Jersey (US)
  • Hackensack Meridian School of Medicine (US)
Corresponding author
Elkabes, Stella
ORCID
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2021-01
Volume
91
Pages
740-755
ISSN
0889-1591 (ISSN-L)
DOI
10.1016/j.bbi.2020.10.007
PMC
PMC7543714
OpenAlex
W3092269026
Cited by
283
References
32
Citations by year
2026: 28 · 2025: 59 · 2024: 52 · 2023: 64 · 2022: 52 · 2021: 28
FWCI
3.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Behavior and Immunity (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
New Jersey Commission on Spinal Cord Research
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
astrocytes, Toll-like receptors, pattern recognition receptors, central nervous system infection, neurodegenerative diseases, central nervous system injury, sterile inflammation, astrocyte heterogeneity, microglia, neuroinflammation
MeSH terms
Animals, Astrocytes, Brain, Central Nervous System, Central Nervous System Diseases, Central Nervous System Infections, Encephalitis, Humans, Immunity, Innate, Neurons, Spinal Cord, Spinal Cord Injuries, Signal Transduction, Microglia, Neurodegenerative Diseases, Receptors, Pattern Recognition, Toll-Like Receptors

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