Microglia and Astrocytes as Drug Targets

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (27 November 2023) | Viewed by 3926

Special Issue Editors


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Guest Editor
Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
Interests: multiple sclerosis; glia; neuroinflammation; myelin; lipid; protein

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Guest Editor
Department of Neurosurgery, Rutgers University, Staged Research Building-Rm 144-145, 661 Hoes Lane West, Piscataway, NJ 08854, USA
Interests: neuroinflammation; glial cells; neurodegenerative diseases; Parkinson’s disease; glial morphology

Special Issue Information

Dear Colleagues,

Recent findings suggest that neuroinflammation is driven by the activation of microglia and astrocytes (gliosis) and escalates with demyelination or neurodegeneration in many neurodegenerative or demyelinating diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). In normal physiological condition, glial cells maintain homeostasis in and provide support to the central nervous system (CNS) and participate in the regulation of neuronal and synaptic functions. Upon activation, microglia and astrocytes can be either beneficial or detrimental based on the level or stages of activation. By enhancing beneficial and/or reducing detrimental aspects of glial activation, amelioration of neuroinflammation, demyelination and neurodegeneration can be achieved, although no such therapeutics exists based on our knowledge. Therefore, there is a crucial need to find new therapeutic products that can modulate glial activation to treat neuroinflammatory and neurodegenerative diseases in the future. This is the focus of this Special Issue, which will collect articles investigating microglia and astrocytes-specific drug candidates.

Dr. Monokesh K. Sen
Dr. Faheem Ullah
Guest Editors

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Keywords

  • neuroinflammation
  • demyelination
  • gliosis
  • neuroprotection
  • neurodegeneration
  • therapeutic drug targets

Published Papers (2 papers)

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Research

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19 pages, 7083 KiB  
Article
Cofilin Inhibitor Improves Neurological and Cognitive Functions after Intracerebral Hemorrhage by Suppressing Endoplasmic Reticulum Stress Related-Neuroinflammation
by Daniyah A. Almarghalani, Ghaith A. Bahader, Mohammad Ali, L. M. Viranga Tillekeratne and Zahoor A. Shah
Pharmaceuticals 2024, 17(1), 114; https://doi.org/10.3390/ph17010114 - 15 Jan 2024
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Abstract
Neuroinflammation after intracerebral hemorrhage (ICH) is a crucial factor that determines the extent of the injury. Cofilin is a cytoskeleton-associated protein that drives neuroinflammation and microglia activation. A novel cofilin inhibitor (CI) synthesized and developed in our lab has turned out to be [...] Read more.
Neuroinflammation after intracerebral hemorrhage (ICH) is a crucial factor that determines the extent of the injury. Cofilin is a cytoskeleton-associated protein that drives neuroinflammation and microglia activation. A novel cofilin inhibitor (CI) synthesized and developed in our lab has turned out to be a potential therapeutic agent for targeting cofilin-mediated neuroinflammation in an in vitro model of ICH and traumatic brain injury. The current study aims to examine the therapeutic potential of CI in a mouse collagenase model of ICH and examine the neurobehavioral outcomes and its mechanism of action. Male mice were subjected to intrastriatal collagenase injection to induce ICH, and sham mice received needle insertion. Various concentrations (25, 50, and 100 mg/kg) of CI were administered to different cohorts of the animals as a single intravenous injection 3 h following ICH and intraperitoneally every 12 h for 3 days. The animals were tested for neurobehavioral parameters for up to 7 days and sacrificed to collect brains for hematoma volume measurement, Western blotting, and immunohistochemistry. Blood was collected for cofilin, TNF-α, and IL-1β assessments. The results indicated that 50 mg/kg CI improved neurological outcomes, reversed post-stroke cognitive impairment, accelerated hematoma resolution, mitigated cofilin rods/aggregates, and reduced microglial and astrocyte activation in mice with ICH. Microglia morphological analysis demonstrated that CI restored the homeostasis ramification pattern of microglia in mice treated with CI. CI suppressed endoplasmic reticulum stress-related neuroinflammation by inhibiting inflammasomes and cell death signaling pathways. We also showed that CI prevented synaptic loss by reviving the pre- and post-synaptic markers. Our results unveil a novel therapeutic approach to treating ICH and open a window for using CI in clinical practice. Full article
(This article belongs to the Special Issue Microglia and Astrocytes as Drug Targets)
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25 pages, 6316 KiB  
Review
Sialic Acid Mimetic Microglial Sialic Acid-Binding Immunoglobulin-like Lectin Agonism: Potential to Restore Retinal Homeostasis and Regain Visual Function in Age-Related Macular Degeneration
by Michael J. Tolentino, Andrew J. Tolentino, Elizabeth M. Tolentino, Anitha Krishnan and Mohamed A. Genead
Pharmaceuticals 2023, 16(12), 1735; https://doi.org/10.3390/ph16121735 - 16 Dec 2023
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Abstract
Age-related macular degeneration (AMD), a leading cause of visual loss and dysfunction worldwide, is a disease initiated by genetic polymorphisms that impair the negative regulation of complement. Proteomic investigation points to altered glycosylation and loss of Siglec-mediated glyco-immune checkpoint parainflammatory and inflammatory homeostasis [...] Read more.
Age-related macular degeneration (AMD), a leading cause of visual loss and dysfunction worldwide, is a disease initiated by genetic polymorphisms that impair the negative regulation of complement. Proteomic investigation points to altered glycosylation and loss of Siglec-mediated glyco-immune checkpoint parainflammatory and inflammatory homeostasis as the main determinant for the vision impairing complications of macular degeneration. The effect of altered glycosylation on microglial maintained retinal para-inflammatory homeostasis and eventual recruitment and polarization of peripheral blood monocyte-derived macrophages (PBMDMs) into the retina can explain the phenotypic variability seen in this clinically heterogenous disease. Restoring glyco-immune checkpoint control with a sialic acid mimetic agonist targeting microglial/macrophage Siglecs to regain retinal para-inflammatory and inflammatory homeostasis is a promising therapeutic that could halt the progression of and improve visual function in all stages of macular degeneration. Full article
(This article belongs to the Special Issue Microglia and Astrocytes as Drug Targets)
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