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January 17, 2026International Journal of Molecular Sciences0 citationsOpen Access

Glial Cells as Key Mediators in the Pathophysiology of Neurodegenerative Diseases

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KBKatarzyna BogusNMNicoletta MarchesiLCLucrezia Irene Maria Campagnoli

Key Points

  • The aim is to explore the role of glial cells in the initiation and progression of neurodegenerative diseases.
  • Review of existing literature on glial cell functions and their implications in neurodegenerative diseases.
  • Analysis of glial responses in conditions like Alzheimer’s, Parkinson’s, and multiple sclerosis.
  • Examination of recent advances in single-cell and spatial omics related to glial heterogeneity.
  • Glial cells play a critical role in neuronal survival and modulate processes like neuroinflammation and proteostasis.
  • Dysregulated glial activity contributes to chronic inflammation and neuronal degeneration.
  • Dynamic shifts in glial phenotypes indicate a complex interplay between protective and harmful roles.

Abstract

Neurodegenerative disorders are characterized by progressive neuronal loss and dysfunction, yet increasing evidence indicates that glial cells are central mediators of both disease initiation and progression. Astrocytes, microglia, and oligodendrocyte lineage cells modulate neuronal survival by regulating neuroinflammation, metabolic support, synaptic maintenance, and proteostasis. However, dysregulated glial responses, including chronic microglial activation, impaired phagocytosis, altered cytokine production, and mitochondrial dysfunction, contribute to persistent inflammation and structural degeneration observed across Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease and multiple sclerosis. Recent advances in single-cell and spatial omics have revealed extensive glial heterogeneity and dynamic shifts between neuroprotective and neurotoxic phenotypes, emphasizing the context-dependent nature of glial activity. This review summarizes current knowledge regarding the multifaceted involvement of glial cells in neurodegenerative disorders.

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Cite This Study

Bogus et al. (2026) studied this question.

synapsesocial.com/papers/696b26d7d2a12237a934a0adhttps://doi.org/10.3390/ijms27020884
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