Inflammation at the Nexus of Neurodegeneration: Cellular Mechanisms, Biomarkers and Therapeutic Targets

A Special Issue of Cells (ISSN 2073-4409) belonging to the section "Cellular Neuroscience".

Deadline for manuscript submissions: 15 December 2026 | Viewed by 1777

Editor


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Guest Editor
School of Science and Technology, University of New England, Armidale, Australia
Interests: neuroscience; neurodegeneration; neuroinflammation; vision; optometry; ophthalmology

Special Issue Information

Dear Colleagues,

Neuroinflammation is increasingly recognised as a central driver, rather than a mere bystander, in diverse neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, retinal degeneration and rare inherited disorders. This Special Issue will highlight cellular and molecular inflammatory mechanisms that shape neuronal vulnerability and resilience, with a particular focus on microglia, astrocytes, peripheral immune cells, and the neurovascular unit. We welcome original research and reviews spanning innate and adaptive immune signaling; inflammasomes and cytokine networks; complement and chemokine pathways; crosstalk between metabolism, mitochondrial stress and inflammation; cell death pathways linked to inflammatory signaling; and the development of inflammatory biomarkers from tissue, CSF, blood and imaging. Studies employing cutting-edge approaches, including single‑cell and spatial-omics, advanced imaging, human stem‑cell or organoid models, and translational or interventional studies, are particularly encouraged. By integrating mechanistic, translational and clinical perspectives, this Special Issue aims to define how targeting inflammation can modify disease course and inform next‑generation neuroprotective therapies.

Dr. Kirstan A. Vessey
Guest Editor

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Keywords

  • neuroinflammation
  • microglia
  • astrocytes
  • neurovascular unit
  • inflammasome
  • cytokine signaling
  • cell death pathways
  • biomarkers
  • retinal degeneration
  • neurodegenerative disease

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Published Papers (2 papers)

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Research

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23 pages, 23160 KB  
Article
Cholinergic Differentiation of Human iPSCs Reveals Early APOE4-Driven Dysregulation of Neuronal Markers, Synaptogenesis and Inflammatory Responses
by Nele Johanne Czaniera, Wiebke Schulten, Katja Nowak, Diana Pschik, Jonas Joneleit, Barbara Kaltschmidt and Christian Kaltschmidt
Cells 2026, 15(12), 1057; https://doi.org/10.3390/cells15121057 - 9 Jun 2026
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Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by progressive memory impairment and cognitive decline. The APOE4 allele represents one of the most prominent genetic risk factors. In this study, we investigated the impact of APOE4 on the cholinergic neuronal development and [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by progressive memory impairment and cognitive decline. The APOE4 allele represents one of the most prominent genetic risk factors. In this study, we investigated the impact of APOE4 on the cholinergic neuronal development and on the neuronal inflammatory response to TNF-α stimulation. To address this, human induced pluripotent stem cells (hiPSCs) carrying a homozygous APOE4 genotype and an isogenic APOE3 control were differentiated into cholinergic-like induced neurons (iNs) by LHX8 overexpression. APOE4 was associated with accelerated early neuronal differentiation, as reflected by earlier downregulation of the progenitor marker Nestin. However, delayed expression of synaptophysin indicated impaired synaptic maturation. Functionally, APOE3 iNs exhibited a robust but temporally regulated response to TNF-α, whereas APOE4 iNs were characterized by a delayed yet sustained induction of inflammatory signaling. Moreover, APOE4 iNs displayed an enhanced stress-associated transcriptional response at early differentiation stages. Collectively, these findings suggest that APOE4 influences both neuronal development and the timing and persistence of inflammatory responses, potentially predisposing cholinergic neurons to later dysfunction in AD. Full article
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Review

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21 pages, 894 KB  
Review
The Ocular Microbiome and Alzheimer’s Disease: Emerging Insights
by Shyam Kumar Mishra, Jerome Ozkan, Feifei Su, Woojin Scott Kim, Mark Willcox and YuHong Fu
Cells 2026, 15(17), 1590; https://doi.org/10.3390/cells15171590 - 1 Sep 2026
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaques, neurofibrillary tau tangles, neuroinflammation, and progressive cognitive decline. Beyond these classical pathological features, emerging evidence implicates microbial dysbiosis as a contributing factor, with the gut and oral microbiomes currently providing the [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaques, neurofibrillary tau tangles, neuroinflammation, and progressive cognitive decline. Beyond these classical pathological features, emerging evidence implicates microbial dysbiosis as a contributing factor, with the gut and oral microbiomes currently providing the strongest evidence for microbiome AD associations. In contrast, the ocular microbiome represents a biologically plausible but largely unexplored candidate whose potential contribution to AD pathogenesis remains hypothetical and requires rigorous investigation. The ocular surface shares embryological, anatomical, and functional connections with the central nervous system, and the retina has emerged as a non-invasive window into neurodegenerative brain changes. Bacterial taxa detected in ocular specimens, including Cutibacterium acnes and Acinetobacter johnsonii, overlap with those reported in some studies of AD brain tissue, prompting speculation about an ocular–brain microbial interface. However, this overlap does not establish microbial trafficking, and no direct evidence currently supports the proposition that ocular microorganisms translocate to, colonize, or contribute causally to AD brain pathology. This review critically appraises the existing evidence, graded by methodological rigor and evidence strength, across gut, oral, nasal, ear, and ocular microbiome compartments. We address the substantial methodological challenges inherent in low-biomass microbiome research, emphasize the importance of distinguishing contamination artifacts from biological signals, and delineate the evidence gaps that separate association from causation. We conclude by proposing a research framework that places the ocular microbiome as an emerging hypothesis warranting experimental validation, rather than an established contributor to AD. Full article
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