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Immunity in Neurodegenerative Diseases: Systemic Immune Imbalance, Neuroinflammation, and Beyond—2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 28 February 2026 | Viewed by 393

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Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia
Interests: adaptive and innate immunity; neuroimmunity; cellular signaling; immunology; T cells
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Special Issue Information

Dear Colleagues,

Although immune reactions in the central nervous system (CNS) were, in the past, uniformly branded as noxious, it is now increasingly clear that the immune system closely monitors the CNS and exerts a major protective role. It does so both from within the CNS parenchyma, primarily through the only resident immune cell there (microglia), and from afar, via numerous peripheral immune cell subsets. The latter can oftentimes act without crossing the blood–brain barrier. This shows the immense power of communication between the immune system and the CNS that operates through numerous passages (the choroid plexus, brain-draining lymph vessels, and skull bone marrow channels), neuroimmune units in the gut and skin, and the vagus nerve, among others. Notably, in many pathologic conditions, the immune system can turn neurotoxic and become the primary source of neuronal damage and ultimately death. Neuroinflammation is being identified as one of the most important pathological hallmarks in different brain pathologies. It can be seen in a wide variety of diseases ranging from brain trauma to neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Recent years have brought new insights into the various neuroprotective and neurotoxic functions exerted not only by the microglia, border-associated macrophages, and (exceptionally limited) adaptive immune cells in the CNS but also by various peripheral immune subsets, including, but not limited to, regulatory CD4 T cells, NK cells, neuromuscular junction macrophages, and mast cells. These two opposite functions have a range of implications in the processes of neurodevelopment, synaptogenesis, neuroplasticity, chronic stress, and neurodegeneration.

We encourage the submission of original research and review articles focused on the following topics:

  • Genetics and molecular mechanisms of neurodegeneration linked to immune functions.
  • The role of CNS-resident immune cells in neuroprotection and neurotoxicity.
  • The systemic immune imbalance in neurodegenerative diseases.
  • The link between ageing and neuroinflammation.
  • Neuroimmune axis.
  • Peripheral vs. central mediators of neuroinflammation.
  • Preventive and therapeutic strategies targeting the immune system in neurodegenerative diseases.

This Special Issue is supervised by Dr. Ivana Munitic, who will be assisted by Dr. Fatema Mustafa Currim (Hall for Discovery and Learning Research, Purdue University, 3rd Floor, RM. 303, West Lafayette, IN 47907, United States).

Dr. Ivana Munitic
Guest Editor

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Keywords

  • neurodegeneration
  • CNS immunosurveillance
  • neuroinflammation
  • neuroimmune axis
  • glia
  • T cells
  • phagocytosis
  • immunomodulation
  • autoimmunity
  • immunodeficiency

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Published Papers (1 paper)

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Research

24 pages, 6934 KB  
Article
Optineurin Shapes Basal and LPS-Induced Transcriptomes in BV2 Microglia
by Sara Cappelli, Josip Peradinovic, Nikolina Mohovic, Purba Mandal, Cristiana Stuani, Alessandra Longo, Jason R. Cannon, Priyanka Baloni, Benedetta Leoni, Tamara Krsmanovic, Katica Stojanov, Gordana Apic, Robert B. Russell, Maurizio Romano, Emanuele Buratti and Ivana Munitic
Int. J. Mol. Sci. 2025, 26(21), 10453; https://doi.org/10.3390/ijms262110453 - 28 Oct 2025
Viewed by 301
Abstract
The OPTN gene, which encodes the adaptor protein optineurin, is genetically linked to amyotrophic lateral sclerosis and frontotemporal dementia, diseases characterized by chronic microglial activation. Optineurin regulates inflammatory signaling, autophagy, and trafficking, but its role in microglia remains incompletely understood. Here, we used [...] Read more.
The OPTN gene, which encodes the adaptor protein optineurin, is genetically linked to amyotrophic lateral sclerosis and frontotemporal dementia, diseases characterized by chronic microglial activation. Optineurin regulates inflammatory signaling, autophagy, and trafficking, but its role in microglia remains incompletely understood. Here, we used bulk RNA sequencing to profile CRISPR-Cas9-mediated optineurin knockout (KO) and wild-type BV2 microglia under basal conditions and upon LPS stimulation. At baseline, optineurin KO altered ~7% of the transcriptome, with a predominant downregulation of type I interferon and antiviral pathways, suggesting its role in maintaining basal immune readiness. LPS stimulation reprogrammed ~35% of genes in wild-type microglia, inducing immune effectors and suppressing cell cycle regulators, whereas in optineurin-deficient cells, the response was blunted with only ~16% of genes changing relative to the KO baseline. Furthermore, LPS-treated optineurin KO microglia notably diverged from LPS-treated wild-type cells, with ~26% differentially expressed genes (DEGs). This included impaired induction of inflammatory programs and persistence of cell cycle-associated transcripts. Most DEGs in LPS-treated KO cells were unique to this condition, highlighting optineurin-dependent pathways specific to inflammatory challenge. Overall, our study provides a systems-level framework for investigating optineurin in microglia and neurodegeneration, establishing it as a key regulator of the microglial transcriptome, with its loss reshaping innate immune and cell cycle programs. Full article
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