The Role of Microglia in Aging and Neurodegenerative Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 25 August 2024 | Viewed by 1954

Special Issue Editor


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Guest Editor
Medical School OWL, Anatomy and Cell Biology, Bielefeld University, 33615 Bielefeld, Germany
Interests: the mechanisms of TGF-beta-mediated modulation of microglia functions under physiological and pathological conditions; microglia development/maturation, microglia functions during postnatal CNS development, and microglia in the aged and diseased CNS are addressed using transgenic mouse models
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Special Issue Information

Dear Colleagues,

Microglia significantly change their morphological and functional features during aging as well as during the course of neurodegenerative diseases, thereby contributing to the onset and progression of several CNS pathologies. However, whether microglia reactivity has beneficial or detrimental effects and consequences seems to depend on the particular disease. Moreover, the crosstalk with peripheral immune cells and the gut–brain axis involved in the regulation of age-dependent and disease-specific microglia reactions are only partially understood. We aim to elucidate different microglia reaction states found in distinct CNS pathologies and their contribution to disease outcomes.

Major questions include how microglia functions are regulated during aging and neurodegenerative processes and which endogenous and exogenous factors might bear therapeutic potential for the treatment of neurodegenerative diseases. Furthermore, the understanding of how the gut–brain axis and metabolic changes regulate the reactivity of microglia in CNS diseases will be a major purpose of this Special Issue.

Submissions of original research and review manuscripts focusing on microglia activation and the role of microglia in neurodegenerative diseases of the brain and spinal cord are welcome. We hope to comprehensively summarize and elucidate the different microglia activation states related to neurodegeneration and hope to increase the overall understanding of microglia in neurodegenerative diseases.

Prof. Dr. Björn Spittau
Guest Editor

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Keywords

  • microglia
  • neurodegenerative diseases
  • disease-associated microglia (DAM)
  • microglia activation
  • Alzheimer's disease
  • Parkinson’s disease
  • ischemic stroke

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Published Papers (2 papers)

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Research

20 pages, 2345 KiB  
Article
Incretin-Based Multi-Agonist Peptides Are Neuroprotective and Anti-Inflammatory in Cellular Models of Neurodegeneration
by Katherine O. Kopp, Yazhou Li, Elliot J. Glotfelty, David Tweedie and Nigel H. Greig
Biomolecules 2024, 14(7), 872; https://doi.org/10.3390/biom14070872 - 19 Jul 2024
Viewed by 764
Abstract
Glucagon-like peptide-1 (GLP-1)-based drugs have been approved by the United States Food and Drug Administration (FDA) and are widely used to treat type 2 diabetes mellitus (T2DM) and obesity. More recent developments of unimolecular peptides targeting multiple incretin-related receptors (“multi-agonists”), including the glucose-dependent [...] Read more.
Glucagon-like peptide-1 (GLP-1)-based drugs have been approved by the United States Food and Drug Administration (FDA) and are widely used to treat type 2 diabetes mellitus (T2DM) and obesity. More recent developments of unimolecular peptides targeting multiple incretin-related receptors (“multi-agonists”), including the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and the glucagon (Gcg) receptor (GcgR), have emerged with the aim of enhancing drug benefits. In this study, we utilized human and mouse microglial cell lines, HMC3 and IMG, respectively, together with the human neuroblastoma SH-SY5Y cell line as cellular models of neurodegeneration. Using these cell lines, we studied the neuroprotective and anti-inflammatory capacity of several multi-agonists in comparison with a single GLP-1 receptor (GLP-1R) agonist, exendin-4. Our data demonstrate that the two selected GLP-1R/GIPR dual agonists and a GLP-1R/GIPR/GcgR triple agonist not only have neurotrophic and neuroprotective effects but also have anti-neuroinflammatory properties, as indicated by the decreased microglial cyclooxygenase 2 (COX2) expression, nitrite production, and pro-inflammatory cytokine release. In addition, our results indicate that these multi-agonists have the potential to outperform commercially available single GLP-1R agonists in neurodegenerative disease treatment. Full article
(This article belongs to the Special Issue The Role of Microglia in Aging and Neurodegenerative Disease)
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18 pages, 6547 KiB  
Article
West Nile Virus-Induced Expression of Senescent Gene Lgals3bp Regulates Microglial Phenotype within Cerebral Cortex
by Artem Arutyunov, Violeta Durán-Laforet, Shenjian Ai, Loris Ferrari, Robert Murphy, Dorothy P. Schafer and Robyn S. Klein
Biomolecules 2024, 14(7), 808; https://doi.org/10.3390/biom14070808 - 8 Jul 2024
Viewed by 807
Abstract
Microglia, the resident macrophages of the central nervous system, exhibit altered gene expression in response to various neurological conditions. This study investigates the relationship between West Nile Virus infection and microglial senescence, focusing on the role of LGALS3BP, a protein implicated in both [...] Read more.
Microglia, the resident macrophages of the central nervous system, exhibit altered gene expression in response to various neurological conditions. This study investigates the relationship between West Nile Virus infection and microglial senescence, focusing on the role of LGALS3BP, a protein implicated in both antiviral responses and aging. Using spatial transcriptomics, RNA sequencing and flow cytometry, we characterized changes in microglial gene signatures in adult and aged mice following recovery from WNV encephalitis. Additionally, we analyzed Lgals3bp expression and generated Lgals3bp-deficient mice to assess the impact on neuroinflammation and microglial phenotypes. Our results show that WNV-activated microglia share transcriptional signatures with aged microglia, including upregulation of genes involved in interferon response and inflammation. Lgals3bp was broadly expressed in the CNS and robustly upregulated during WNV infection and aging. Lgals3bp-deficient mice exhibited reduced neuroinflammation, increased homeostatic microglial numbers, and altered T cell populations without differences in virologic control or survival. These data indicate that LGALS3BP has a role in regulating neuroinflammation and microglial activation and suggest that targeting LGALS3BP might provide a potential route for mitigating neuroinflammation-related cognitive decline in aging and post-viral infections. Full article
(This article belongs to the Special Issue The Role of Microglia in Aging and Neurodegenerative Disease)
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