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Cited by 69Advanced Glycation End Products researchNeuroinflammation and Neurodegeneration MechanismsBarrier Structure and Function Studies

The Receptor for Advanced Glycation End Products (RAGE) and DIAPH1: Implications for vascular and neuroinflammatory dysfunction in disorders of the central nervous system

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MacLean, Michael, Derk, Julia, Ruiz, Henry H., Juranek, Judyta K., Ramasamy, Ravichandran, Schmidt, Ann Marie·2019·Neurochemistry International
DOI 10.1016/j.neuint.2019.03.012PMC PMC10976457
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Abstract

The Receptor for Advanced Glycation End Products (RAGE) is expressed by multiple cell types in the brain and spinal cord that are linked to the pathogenesis of neurovascular and neurodegenerative disorders, including neurons, glia (microglia and astrocytes) and vascular cells (endothelial cells, smooth muscle cells and pericytes). Mounting structural and functional evidence implicates the interaction of the RAGE cytoplasmic domain with the formin, Diaphanous1 (DIAPH1), as the key cytoplasmic hub for RAGE ligand-mediated activation of cellular signaling. In aging and diabetes, the ligands of the receptor abound, both in the central nervous system (CNS) and in the periphery. Such accumulation of RAGE ligands triggers multiple downstream events, including upregulation of RAGE itself. Once set in motion, cell intrinsic and cell-cell communication mechanisms, at least in part via RAGE, trigger dysfunction in the CNS. A key outcome of endothelial dysfunction is reduction in cerebral blood flow and increased permeability of the blood brain barrier, conditions that facilitate entry of activated leukocytes into the CNS, thereby amplifying primary nodes of CNS cellular stress. This contribution details a review of the ligands of RAGE, the mechanisms and consequences of RAGE signal transduction, and cites multiple examples of published work in which RAGE contributes to the pathogenesis of neurovascular perturbation. Insights into potential therapeutic modalities targeting the RAGE signal transduction axis for disorders of CNS vascular dysfunction and neurodegeneration are also discussed.

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  • In aging and diabetes, levels of RAGE ligands are increased in both the CNS and the periphery, which upregulate expression of RAGE receptor and induce multiple downstream events.

    “In aging and diabetes, the levels of RAGE ligands are increased in both the CNS and the periphery, which upregulate the expression of RAGE receptor and induces multiple downstream events.324”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [324]

  • In the CNS, RAGE is expressed by multiple cell types, including microglia, astrocytes, neurons, pericytes and endothelial cells.

    “In the CNS, RAGE is expressed by multiple cell types, including microglia, astrocytes, neurons, pericytes and endothelial cells.324”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [324]

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Cited by

Sorted by citations

Authors
MacLean, M., Derk, J., Ruiz, H. H., Juranek, J. K., Ramasamy, R., & Schmidt, A. M.
Affiliations
  • New York University (US)
  • NYU Langone Health (US)
Corresponding author
Schmidt, Ann Marie
ORCID
Venue
Neurochemistry International
Publisher
Elsevier BV
Published
2019-06
Volume
126
Pages
154-164
ISSN
0197-0186 (ISSN-L)
DOI
10.1016/j.neuint.2019.03.012
PMC
PMC10976457
OpenAlex
W2923098009
Cited by
69
References
15
Citations by year
2026: 12 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 14 · 2020: 10 · 2019: 3
FWCI
1.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurochemistry International (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • United States Public Health Service
  • American Heart Association
  • JDRF
  • American Diabetes Association
  • Alzheimer's Association
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
receptor for advanced glycation end products, RAGE, formins, RAGE ligands, neurovascular dysfunction, neuroinflammation, neurodegeneration, endothelial dysfunction, blood-brain barrier permeability, cerebral blood flow, microglia, astrocytes, pericytes, aging, diabetes mellitus
MeSH terms
Receptor for Advanced Glycation End Products, Formins, Animals, Central Nervous System Diseases, Humans, Vascular Diseases, Glycation End Products, Advanced, Inflammation Mediators, Neurodegenerative Diseases

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