Cited by 236Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsInflammasome and immune disorders

Danger-associated molecular patterns in Alzheimer’s disease

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Venegas, Carmen, Heneka, Michael T·2017·Journal of Leukocyte Biology

Abstract

Pathogen-associated molecular patterns (PAMPs) and endogenous “danger” signals, known as danger-associated molecular patterns (DAMPs), released from cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved pattern recognition receptors (PRRs). Both PAMPs and DAMPs directly induce proinflammatory cascades and trigger the formation of the inflammasome, mediating the release of cytokines. Here, we highlight the role of DAMPs, including amyloid β (Aβ), high-mobility group box 1 (HMGB1), the S100 family proteins, chromogranin A, and nucleic acids, in the innate-immune activation during the course of Alzheimer disease (AD), the most frequent neurodegenerative disorder.

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Crossref · 10.1189/jlb.3mr0416-204r

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  • DAMPs released from damaged brain cells (mtDNA, HMGB1, S100 proteins, chromogranin A, ATP, uric acid) trigger neuroinflammation by activating PRRs (TLRs, RAGE, NLRs, P2Y receptors) expressed on cerebral myeloid cells or intracellularly.

    “In addition to aggregates, tissue injury also induces the extracellular release of DAMPs, such as mitochondrial DNA (mtDNA), high mobility group box 1 (HMGB1), S100 proteins, chromogranin A, adenosine 5′-triphosphate (ATP), and uric acid, from damaged brain cells. These DAMPs trigger neuroinflammation by activating pattern recognition receptors (PRRs), including TLRs, RAGE, NLRs, P2Y receptors”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [48]

    The Introduction lists all six named substances as DAMPs, and DAMPs ORIGIN describes their release after cell injury. DAMPs IN AD and PRRs support inflammatory signaling through TLRs, RAGE and intracellular NLRs, including receptors in microglia. The cited passages do not identify P2Y receptors as part of this mechanism. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • PRRs bind different species of amyloid-beta with varying affinities.

    “PRRs bind to different species of Aβ with various affinities (71).”

    From Microglia in Alzheimer's disease (2017) · cites this paper as [71]

  • In Alzheimer's disease, Aβ can act as a danger-associated molecular pattern, and its interaction with microglia creates an oxidative and neuroinflammatory environment through increased production of reactive oxygen species and release of proinflammatory cytokines.

    “In AD, Aβ can act as DAMP and its interaction with microglia creates an oxidative and neuroinflammatory environment through an increased production of ROS and release of proinflammatory cytokines [107].”

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Authors
Venegas, C., & Heneka, M. T.
Affiliations
University of Bonn (DE)
Corresponding author
Heneka, Michael T
Venue
Journal of Leukocyte Biology
Published
2016-10-21
Volume
101
Issue
1
Pages
87-98
ISSN
  • 0741-5400 (ISSN-L)
  • 1938-3673
OpenAlex
W2534771646
Cited by
236
References
156
Citations by year
2026: 24 · 2025: 26 · 2024: 29 · 2023: 25 · 2022: 29 · 2021: 30 · 2020: 30 · 2019: 15 · 2018: 15 · 2017: 11
FWCI
1.20
Type
journal article
Language
en
Open access
Locations
  • Journal of Leukocyte Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Open Repository and Bibliography (University of Luxembourg) (submittedVersion)
  • DZNE Pub (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
damage-associated molecular patterns, Alzheimer's disease, innate immunity, pattern recognition receptors, pathogen-associated molecular patterns, inflammasome, amyloid-beta, HMGB1, S-100 protein, chromogranin A, nucleic acids, neuroinflammation, cytokine production
MeSH terms
Alarmins, Alzheimer Disease, Animals, Humans, Inflammation, Models, Biological, Receptors, Pattern Recognition, Molecular Targeted Therapy

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