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Cited by 275Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

The role of Toll-like receptors and neuroinflammation in Parkinson’s disease

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Heidari, Arash, Yazdanpanah, Niloufar, Rezaei, Nima·2022·Journal of Neuroinflammation
DOI 10.1186/s12974-022-02496-wPMC PMC9172200
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Abstract

Background: Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, characterized by motor and non-motor symptoms, significantly affecting patients’ life. Pathologically, PD is associated with the extensive degeneration of dopaminergic neurons in various regions of the central nervous system (CNS), specifically the substantia nigra. This neuronal loss is accompanied by the aggregation of misfolded protein, named α-synuclein. Main text: Recent studies detected several clues of neuroinflammation in PD samples using postmortem human PD brains and various PD animal models. Some evidence of neuroinflammation in PD patients included higher levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF), presence of activated microglia in various brain regions such as substantia nigra, infiltration of peripheral inflammatory cells in affected brain regions, and altered function of cellular immunity like monocytes phagocytosis defects. On the other side, Toll-like receptors (TLRs) are innate immune receptors primarily located on microglia, as well as other immune and non-immune cells, expressing pivotal roles in recognizing exogenous and endogenous stimuli and triggering inflammatory responses. Most studies indicated an increased expression of TLRs in the brain and peripheral blood cells of PD samples. Besides, this upregulation was associated with excessive neuroinflammation followed by neurodegeneration in affected regions. Therefore, evidence proposed that TLR-mediated neuroinflammation might lead to a dopaminergic neural loss in PD patients. In this regard, TLR2, TLR4, and TLR9 have the most prominent roles. Conclusion: Although the presence of inflammation in acute phases of PD might have protective effects concerning the clearance of α-synuclein and delaying the disease advancement, the chronic activation of TLRs and neuroinflammation might lead to neurodegeneration, resulting in the disease progression. Therefore, this study aimed to review additional evidence of the contribution of TLRs and neuroinflammation to PD pathogenesis, with the hope that TLRs could serve as novel disease-modifying therapeutic targets in PD patients in the future.

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  • α-synuclein can act as a DAMP to activate microglia through TLRs receptors.

    “α-synuclein can act as a DAMP to activate microglia through TLRs receptors, thus blocking TLR signaling may be a therapeutic strategy for attenuating PD.565”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [565]

  • Blocking TLR signaling may be a therapeutic strategy for attenuating PD.

    “thus blocking TLR signaling may be a therapeutic strategy for attenuating PD.565”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [565]

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Cited by

Sorted by citations

Authors
Heidari, A., Yazdanpanah, N., & Rezaei, N.
Affiliations
Universal Scientific Education and Research Network (IR)
Corresponding author
Rezaei, Nima
ORCID
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2022-06-06
Volume
19
Issue
1
Pages
135-135
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/s12974-022-02496-w
PMC
PMC9172200
OpenAlex
W4281787231
Cited by
275
References
23
Citations by year
2026: 63 · 2025: 80 · 2024: 78 · 2023: 48 · 2022: 6
FWCI
5.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
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
Parkinson's disease, Toll-like receptors, neuroinflammation, TLR2, TLR4, TLR9, microglia, dopaminergic neuron loss, substantia nigra, alpha-synuclein, inflammatory cytokines, neurodegeneration
MeSH terms
Neuroinflammatory Diseases, Animals, Humans, Parkinson Disease, Substantia Nigra, Microglia, Toll-Like Receptors, alpha-Synuclein

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