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Cells
Special Issues
Emerging Roles of Glial Cells in Human Health and Disease
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Emerging Roles of Glial Cells in Human Health and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 22705

Special Issue Editors

Prof. Dr. Dan Frenkel

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Guest Editor
Department of Neurobiology, Faculty of Life Sciences, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
Interests: neuroinflammation; glial cells; neurodegenerative diseases
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Menachem Hanani

E-Mail Website
Guest Editor
Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Jerusalem 91240, Israel
Interests: satellite glia; pain; autonomic nervous system

Special Issue Information

Dear Colleagues,

Glial cells play an important role in maintaining neuronal activity and homeostasis in all parts of the nervous system. The term 'glia' covers different types of cells that are located in both the central nervous system, such as astrocytes, oligodendrocytes, ependymal and microglia, and in the peripheral nervous system, such as satellite glial cells, Schwann cells and enteric glia. There is a diversity of subtypes within these groups, and recent methodological advances have enabled the identification of heterogeneities in gene expression within each glial family. Furthermore, changes in the gene impression in glial cells were associated with the development of neurodegenerative diseases such as Alzheimer’s disease. The roles of glial cells under normal and disease states have been studied in animal models for many years, and this research has contributed greatly to the field of neuroscience. However, this important research was carried out mostly on rodents, and may not represent accurately the human nervous system. We therefore believe that it is timely to present current advances in the study of glial cells in humans under various conditions. Understanding glial complexity and activity in humans may pave the way for novel therapeutic interventions to treat currently uncurable diseases. This Special Issue is entitled: “Emerging Roles of Glial Cells in Human Health and Disease”. It will include original research and review papers focusing on this topic.

Please find below suggested topics:

  • Satellite glial cells in human disease;
  • Animal models of human diseases associated with glial cells;
  • Enteric glia and microbiome;
  • Glial cells in neurodegenerative diseases;
  • Glial cells in stroke and trauma;
  • Glial cells in retinal disease;
  • Glia in demyelinating disease (MS, Charcot–Marie–Tooth disease, Guillain–Barre, etc.);
  • Glia cells in hearing problems;
  • Glia–neuron axis;
  • Glia cells in sleep disorders;
  • Glial cells in psychiatric disorders;
  • Infectious diseases and glia.

Prof. Dr. Dan Frenkel
Prof. Dr. Menachem Hanani
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neurodegenerative diseases
  • glia cells
  • astrocyte
  • microglia
  • stroke
  • pain
  • epilepsy
  • trauma
  • demyelinating diseases’ inflammatory diseases
  • satellite glia
  • Schwann cells
  • enteric glia

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Published Papers (9 papers)

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Research

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15 pages, 7382 KiB  
Article
Pharmacological Inhibition of Microglial Proliferation Supports Blood–Brain Barrier Integrity in Experimental Autoimmune Encephalomyelitis
by Nozha Borjini, Mercedes Fernandez, Luciana Giardino, Lydia Sorokin and Laura Calzà
Cells 2025, 14(6), 414; https://doi.org/10.3390/cells14060414 - 12 Mar 2025
Viewed by 589
Abstract
Blood–brain barrier dysfunction (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). We have previously shown that blocking microglial proliferation using GW2580, a selective inhibitor of CSF1R (Colony stimulating factor 1 receptor), reduced disease progression [...] Read more.
Blood–brain barrier dysfunction (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). We have previously shown that blocking microglial proliferation using GW2580, a selective inhibitor of CSF1R (Colony stimulating factor 1 receptor), reduced disease progression and severity and prevented the relapse phase. However, whether this was due to effects of GW2580 on the functional integrity of the BBB was not determined. Therefore, here, we examine BBB properties in rats during EAE under GW2580 treatment. Our data suggest that blocking early microglial proliferation through selective targeting of CSF1R signaling has a therapeutic effect in EAE by protecting BBB integrity and reducing peripheral immune cell infiltration. Taken together, our results identify a novel mechanism underlying the effects of GW2580, which could offer a novel therapy for MS. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
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Review

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21 pages, 3403 KiB  
Review
The Role of Exercise on Glial Cell Activity in Neuropathic Pain Management
by Willians Fernando Vieira, Caroline C. Real, Daniel Oliveira Martins and Marucia Chacur
Cells 2025, 14(7), 487; https://doi.org/10.3390/cells14070487 - 24 Mar 2025
Viewed by 835
Abstract
Chronic pain is a widespread global health problem with profound socioeconomic implications, affecting millions of people of all ages. Glial cells (GCs) in pain pathways play essential roles in the processing of pain signals. Dysregulation of GC activity contributes to chronic pain states, [...] Read more.
Chronic pain is a widespread global health problem with profound socioeconomic implications, affecting millions of people of all ages. Glial cells (GCs) in pain pathways play essential roles in the processing of pain signals. Dysregulation of GC activity contributes to chronic pain states, making them targets for therapeutic interventions. Non-pharmacological approaches, such as exercise, are strongly recommended for effective pain management. This review examines the link between exercise, regular physical activity (PA), and glial cell-mediated pain processing, highlighting its potential as a strategy for managing chronic pain. Exercise not only improves overall health and quality of life but also influences the function of GCs. Recent research highlights the ability of exercise to mitigate neuroinflammatory responses and modulate the activity of GCs by reducing the activation of microglia and astrocytes, as well as modulating the expression biomarkers, thereby attenuating pain hypersensitivity. Here, we summarize new insights into the role of exercise as a non-pharmacological intervention for the relief of chronic pain. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
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27 pages, 1617 KiB  
Review
The Role of Glial Cells in the Pathophysiology of Epilepsy
by Filiz Onat, My Andersson and Nihan Çarçak
Cells 2025, 14(2), 94; https://doi.org/10.3390/cells14020094 - 10 Jan 2025
Viewed by 2292
Abstract
Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly impacting individuals worldwide. Current treatments are often ineffective for a third of patients and can cause severe side effects, necessitating new therapeutic approaches. Glial cells, particularly astrocytes, microglia, and oligodendrocytes, are emerging [...] Read more.
Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly impacting individuals worldwide. Current treatments are often ineffective for a third of patients and can cause severe side effects, necessitating new therapeutic approaches. Glial cells, particularly astrocytes, microglia, and oligodendrocytes, are emerging as crucial targets in epilepsy management. Astrocytes regulate neuronal homeostasis, excitability, and synaptic plasticity, playing key roles in maintaining the blood–brain barrier (BBB) and mediating neuroinflammatory responses. Dysregulated astrocyte functions, such as reactive astrogliosis, can lead to abnormal neuronal activity and seizure generation. They release gliotransmitters, cytokines, and chemokines that may exacerbate or mitigate seizures. Microglia, the innate immune cells of the CNS, contribute to neuroinflammation, glutamate excitotoxicity, and the balance between excitatory and inhibitory neurotransmission, underscoring their dual role in seizure promotion and protection. Meanwhile, oligodendrocytes, primarily involved in myelination, also modulate axonal excitability and contribute to the neuron–glia network underlying seizure pathogenesis. Understanding the dynamic interactions of glial cells with neurons provides promising avenues for novel epilepsy therapies. Targeting these cells may lead to improved seizure control and better clinical outcomes, offering hope for patients with refractory epilepsy. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
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20 pages, 404 KiB  
Review
CHI3L1 in Multiple Sclerosis—From Bench to Clinic
by Izabela Jatczak-Pawlik, Anna Jurewicz, Małgorzata Domowicz, Alicja Ewiak-Paszyńska and Mariusz Stasiołek
Cells 2024, 13(24), 2086; https://doi.org/10.3390/cells13242086 - 17 Dec 2024
Cited by 1 | Viewed by 1074
Abstract
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with a complex and not fully understood etiopathological background involving inflammatory and neurodegenerative processes. CHI3L1 has been implicated in pathological conditions such as inflammation, injury, and neurodegeneration, and is [...] Read more.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with a complex and not fully understood etiopathological background involving inflammatory and neurodegenerative processes. CHI3L1 has been implicated in pathological conditions such as inflammation, injury, and neurodegeneration, and is likely to play a role in the physiological development of the CNS. CHI3L1 is primarily produced by CNS macrophages, microglia, and activated astrocytes. The CHI3L1 expression pattern in MS lesions might support the important role of astrocytes in modulating inflammatory processes in this disease. The potential applications of CHI3L1 as a biomarker in MS are multifactorial. The measurement of CHI3L1 in body fluids might find its role in the early diagnosis of MS. In further stages, the monitoring of CHI3L1 levels might provide information on disease severity and progression, enabling a better adjustment of therapeutic strategies. Importantly, CHI3L1 might potentially serve as a marker of ongoing glial activation, reflecting the dynamic response of the CNS cells to the inflammatory processes in MS. Although preliminary findings have been promising, further research is needed to validate the utility of CHI3L1 measurements in the diagnosis and prediction of the progression of MS. Additionally, comparisons with other biomarkers might be useful in clinical practice. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
14 pages, 1624 KiB  
Review
Sex Differences in Astrocyte Activity
by Elisa Gozlan, Yarden Lewit-Cohen and Dan Frenkel
Cells 2024, 13(20), 1724; https://doi.org/10.3390/cells13201724 - 18 Oct 2024
Cited by 3 | Viewed by 2589
Abstract
Astrocytes are essential for maintaining brain homeostasis. Alterations in their activity have been associated with various brain pathologies. Sex differences were reported to affect astrocyte development and activity, and even susceptibility to different neurodegenerative diseases. This review aims to summarize the current knowledge [...] Read more.
Astrocytes are essential for maintaining brain homeostasis. Alterations in their activity have been associated with various brain pathologies. Sex differences were reported to affect astrocyte development and activity, and even susceptibility to different neurodegenerative diseases. This review aims to summarize the current knowledge on the effects of sex on astrocyte activity in health and disease. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
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20 pages, 3219 KiB  
Review
hPSC-Derived Astrocytes at the Forefront of Translational Applications in Neurological Disorders
by Vukasin M. Jovanovic, Kendall T. Mesch and Carlos A. Tristan
Cells 2024, 13(11), 903; https://doi.org/10.3390/cells13110903 - 24 May 2024
Cited by 1 | Viewed by 2088
Abstract
Astrocytes, the most abundant glial cell type in the brain, play crucial roles in maintaining homeostasis within the central nervous system (CNS). Impairment or abnormalities of typical astrocyte functions in the CNS serve as a causative or contributing factor in numerous neurodevelopmental, neurodegenerative, [...] Read more.
Astrocytes, the most abundant glial cell type in the brain, play crucial roles in maintaining homeostasis within the central nervous system (CNS). Impairment or abnormalities of typical astrocyte functions in the CNS serve as a causative or contributing factor in numerous neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. Currently, disease-modeling and drug-screening approaches, primarily focused on human astrocytes, rely on human pluripotent stem cell (hPSC)-derived astrocytes. However, it is important to acknowledge that these hPSC-derived astrocytes exhibit notable differences across studies and when compared to their in vivo counterparts. These differences may potentially compromise translational outcomes if not carefully accounted for. This review aims to explore state-of-the-art in vitro models of human astrocyte development, focusing on the developmental processes, functional maturity, and technical aspects of various hPSC-derived astrocyte differentiation protocols. Additionally, it summarizes their successful application in modeling neurological disorders. The discussion extends to recent advancements in the large-scale production of human astrocytes and their application in developing high-throughput assays conducive to therapeutic drug discovery. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
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37 pages, 3650 KiB  
Review
Emerging Role of ABC Transporters in Glia Cells in Health and Diseases of the Central Nervous System
by Maria Villa, Jingyun Wu, Stefanie Hansen and Jens Pahnke
Cells 2024, 13(9), 740; https://doi.org/10.3390/cells13090740 - 24 Apr 2024
Cited by 8 | Viewed by 3644
Abstract
ATP-binding cassette (ABC) transporters play a crucial role for the efflux of a wide range of substrates across different cellular membranes. In the central nervous system (CNS), ABC transporters have recently gathered significant attention due to their pivotal involvement in brain physiology and [...] Read more.
ATP-binding cassette (ABC) transporters play a crucial role for the efflux of a wide range of substrates across different cellular membranes. In the central nervous system (CNS), ABC transporters have recently gathered significant attention due to their pivotal involvement in brain physiology and neurodegenerative disorders, such as Alzheimer’s disease (AD). Glial cells are fundamental for normal CNS function and engage with several ABC transporters in different ways. Here, we specifically highlight ABC transporters involved in the maintenance of brain homeostasis and their implications in its metabolic regulation. We also show new aspects related to ABC transporter function found in less recognized diseases, such as Huntington’s disease (HD) and experimental autoimmune encephalomyelitis (EAE), as a model for multiple sclerosis (MS). Understanding both their impact on the physiological regulation of the CNS and their roles in brain diseases holds promise for uncovering new therapeutic options. Further investigations and preclinical studies are warranted to elucidate the complex interplay between glial ABC transporters and physiological brain functions, potentially leading to effective therapeutic interventions also for rare CNS disorders. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
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23 pages, 750 KiB  
Review
Human Glial Cells as Innovative Targets for the Therapy of Central Nervous System Pathologies
by Giulia Magni, Benedetta Riboldi and Stefania Ceruti
Cells 2024, 13(7), 606; https://doi.org/10.3390/cells13070606 - 30 Mar 2024
Cited by 6 | Viewed by 3774
Abstract
In vitro and preclinical in vivo research in the last 35 years has clearly highlighted the crucial physiopathological role of glial cells, namely astrocytes/microglia/oligodendrocytes and satellite glial cells/Schwann cells in the central and peripheral nervous system, respectively. Several possible pharmacological targets to various [...] Read more.
In vitro and preclinical in vivo research in the last 35 years has clearly highlighted the crucial physiopathological role of glial cells, namely astrocytes/microglia/oligodendrocytes and satellite glial cells/Schwann cells in the central and peripheral nervous system, respectively. Several possible pharmacological targets to various neurodegenerative disorders and painful conditions have therefore been successfully identified, including receptors and enzymes, and mediators of neuroinflammation. However, the translation of these promising data to a clinical setting is often hampered by both technical and biological difficulties, making it necessary to perform experiments on human cells and models of the various diseases. In this review we will, therefore, summarize the most relevant data on the contribution of glial cells to human pathologies and on their possible pharmacological modulation based on data obtained in post-mortem tissues and in iPSC-derived human brain cells and organoids. The possibility of an in vivo visualization of glia reaction to neuroinflammation in patients will be also discussed. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
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21 pages, 4220 KiB  
Review
Satellite Glial Cells in Human Disease
by Menachem Hanani
Cells 2024, 13(7), 566; https://doi.org/10.3390/cells13070566 - 23 Mar 2024
Cited by 6 | Viewed by 4228
Abstract
Satellite glial cells (SGCs) are the main type of glial cells in sensory ganglia. Animal studies have shown that these cells play essential roles in both normal and disease states. In a large number of pain models, SGCs were activated and contributed to [...] Read more.
Satellite glial cells (SGCs) are the main type of glial cells in sensory ganglia. Animal studies have shown that these cells play essential roles in both normal and disease states. In a large number of pain models, SGCs were activated and contributed to the pain behavior. Much less is known about SGCs in humans, but there is emerging recognition that SGCs in humans are altered in a variety of clinical states. The available data show that human SGCs share some essential features with SGCs in rodents, but many differences do exist. SGCs in DRG from patients suffering from common painful diseases, such as rheumatoid arthritis and fibromyalgia, may contribute to the pain phenotype. It was found that immunoglobulins G (IgG) from fibromyalgia patients can induce pain-like behavior in mice. Moreover, these IgGs bind preferentially to SGCs and activate them, which can sensitize the sensory neurons, causing nociception. In other human diseases, the evidence is not as direct as in fibromyalgia, but it has been found that an antibody from a patient with rheumatoid arthritis binds to mouse SGCs, which leads to the release of pronociceptive factors from them. Herpes zoster is another painful disease, and it appears that the zoster virus resides in SGCs, which acquire an abnormal morphology and may participate in the infection and pain generation. More work needs to be undertaken on SGCs in humans, and this review points to several promising avenues for better understanding disease mechanisms and developing effective pain therapies. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
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