The Role of Astrocytes in the Inflammatory Response in Neurodiseases

Abstract

ABSTRACT Astrocytes have emerged as central regulators of neuroinflammation, extending far beyond their traditional roles as structural and metabolic support cells. In neurological disorders, astrocytes undergo reactive remodeling that encompasses morphological, transcriptional, metabolic, and functional changes. Rather than fitting into a fixed A1/A2 dichotomy, reactive astrocytes exist along a disease‐, region‐, and stage‐dependent continuum shaped by local pathology and intercellular crosstalk. This review summarizes how astrocytes contribute to neuroinflammatory processes in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, central nervous system injury, infection, multiple sclerosis, epilepsy, and autism spectrum disorder. We highlight convergent mechanisms, including cytokine and chemokine release, complement activation, glutamate and ion homeostasis disruption, oxidative stress, metabolic reprogramming, and blood‐brain barrier regulation, while emphasizing disease‐specific astrocytic programs. We further discuss astrocyte interactions with microglia, neurons, oligodendrocytes, endothelial cells, and peripheral immune cells, as well as key regulatory pathways, epigenetic remodeling, and lipid‐dependent metabolic signaling. Finally, we evaluate current and emerging astrocyte‐targeted therapeutic strategies, including metabolic modulation, receptor targeting, gene editing, nanodelivery, and gut–brain axis interventions. Defining functionally validated astrocyte states and developing biomarker‐guided, stage‐adaptive therapies may enable more precise intervention in neuroinflammatory and neurodegenerative diseases.