Astrocyte Dynamics in Neurodegenerative Disease Mechanisms

Astrocytes, the most abundant glial cells in the central nervous system, are pivotal regulators of neuronal homeostasis, synaptic function and metabolic support. In neurodegenerative diseases, astrocytes undergo dynamic transformations that can be both protective and deleterious. Under stress or injury, they adopt a reactive phenotype characterised by altered morphology, gene expression and secretory profile. These changes influence protein aggregation, inflammatory signalling, neurotransmitter clearance and metabolic coupling. In Alzheimer’s disease, for example, reactive astrocytes modulate amyloid-β deposition through shifts in autophagy‐related pathways and cytokine release, while in Parkinson’s disease they may affect α-synuclein spread and dopaminergic neuronal resilience. In amyotrophic lateral sclerosis and Huntington’s disease, astrocyte dysfunction contributes to excitotoxicity via impaired glutamate uptake and disrupted ion homeostasis. Interactions with microglia and the vasculature further shape disease progression. Emerging evidence highlights astrocyte heterogeneity, with distinct subtypes exerting region‐specific effects and temporal shifts from neuroprotective to neurotoxic states. Targeting key astrocyte signalling nodes—such as autophagic flux, cytokine networks and metabolic pathways—offers promising avenues for intervention across multiple neurodegenerative conditions.

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Astrocyte Dynamics in Neurodegenerative Disease Mechanisms publication trend

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Technical terms

Reactive astrocyte: An astrocyte that has adopted an activated phenotype in response to injury or disease, characterised by changes in morphology and gene expression.

Astrogliosis: The process of astrocyte hypertrophy, proliferation and upregulation of intermediate filaments (e.g. GFAP) during central nervous system pathology.

Autophagic flux: The dynamic sequence of events in autophagy, from autophagosome formation to lysosomal degradation of cellular components.

Amyloid-β (Aβ): A peptide derived from amyloid precursor protein that aggregates into extracellular plaques, a hallmark of Alzheimer’s disease.

Neuroinflammation: The inflammatory response within the central nervous system involving glial cells and pro-inflammatory mediators.

References

1. Astrocytic autophagy plasticity modulates Aβ clearance and cognitive function in Alzheimer’s disease. Molecular Neurodegeneration (2024).
2. Pathological phenotypes of astrocytes in Alzheimer’s disease. Experimental & Molecular Medicine (2024).
3. Reactive Astrocytes in Neurodegenerative Diseases. Aging and Disease (2019).
4. Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease. Journal of Neuroinflammation (2022).