Microglial Function in Neuroinflammatory Disorders

Microglia are the principal innate immune cells of the central nervous system and perform essential roles in tissue surveillance, synaptic remodelling and the clearance of debris. In healthy brain they adopt a ramified morphology and support homeostasis through trophic factor release and phagocytosis of apoptotic cells. Upon encountering danger signals—such as aggregated proteins, damaged neurons or infiltrating pathogens—they undergo dynamic phenotypic changes marked by alterations in gene expression, metabolic state and receptor profiles. This activation spectrum ranges from pro-inflammatory programmes, characterised by secretion of cytokines and reactive oxygen species, to alternative states that promote resolution and tissue repair. In neuroinflammatory disorders including Alzheimer’s disease, Parkinson’s disease and multiple sclerosis, dysregulated microglial responses contribute both to neuronal injury and to attempts at tissue reconstruction. Key molecular pathways—such as NFκB, MAPK cascades and signal transducer and activator of transcription (STAT) networks—coordinate inflammatory gene expression, while epigenetic mechanisms and microRNA circuits fine-tune microglial plasticity. Interactions with astrocytes, oligodendrocytes and peripheral immune cells further shape the inflammatory milieu. Targeting microglial function thus represents a promising therapeutic avenue to attenuate neurodegeneration, promote remyelination and restore normal neural circuitry.

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Microglial Function in Neuroinflammatory Disorders publication trend

The graph below shows the total number of articles in microglial function in neuroinflammatory disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Microglia: Resident macrophage-like immune cells of the central nervous system responsible for surveillance, phagocytosis and modulation of inflammation.

Neuroinflammation: Inflammatory processes within the brain or spinal cord involving activation of glial cells and infiltration of peripheral immune components.

Cytokines: Small secreted proteins (for example interleukins or tumour necrosis factor) that mediate intercellular communication in immune responses.

Phagocytosis: The cellular process by which microglia engulf and digest pathogens, debris and apoptotic cells.

Phenotypic plasticity: The ability of microglia to adopt distinct functional states (pro-inflammatory, anti-inflammatory, repair-oriented) in response to environmental cues.

Epigenetics: Heritable changes in gene expression caused by DNA methylation, histone modifications or non-coding RNAs, without alteration of the DNA sequence.

MAPK (mitogen-activated protein kinase): Intracellular signalling enzymes that transduce external stimuli into specific gene expression programmes, often implicated in inflammatory responses.

NFκB (nuclear factor kappa B): A transcription factor complex that regulates expression of numerous pro-inflammatory genes upon activation by stress or pathogenic signals.

Mesenchymal stem cell: Multipotent stromal cells capable of differentiating into various lineages and releasing immunomodulatory factors, exploited for cell-free therapeutic approaches.

References

1. Mesenchymal Stem Cells-based Cell-free Therapy Targeting Neuroinflammation. Aging and Disease (2023).
2. Microglia and neuroinflammation: a pathological perspective. Journal of Neuroinflammation (2004).
3. The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory genes in microglia. Journal of Molecular Medicine (2013).
4. Epigenetics Control Microglia Plasticity. Frontiers in Cellular Neuroscience (2018).
5. Involvement of NFƙB and MAPK signaling pathways in the preventive effects of Ganoderma lucidum on the inflammation of BV-2 microglial cells induced by LPS. Journal of Neuroimmunology (2020).
6. Novel Molecular Insights into Classical and Alternative Activation States of Microglia as Revealed by Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)-based Proteomics* [S]. Molecular & Cellular Proteomics (2015).