Astrocytic Interactions in Neurodegenerative Disease Pathogenesis

Astrocytes, the most abundant glial cells in the central nervous system, perform essential roles in maintaining neuronal homeostasis, regulating synaptic transmission, and supporting the blood–brain barrier. In neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis, astrocytes undergo phenotypic transformations that can either protect neurons or contribute to pathology. Reactive astrogliosis, a hallmark of injury, involves morphological and functional changes that alter cytokine release, glutamate uptake and redox balance. Astrocytes can internalise misfolded proteins such as α-synuclein and amyloid-β, either facilitating their clearance via endocytic and autophagic pathways or inadvertently propagating aggregate spread. Crosstalk between astrocytes, microglia and neurons amplifies inflammatory circuits and shapes the local microenvironment. Dysregulated astrocytic calcium signalling, impaired metabolic support and compromised blood–brain barrier integrity further exacerbate neuronal vulnerability. Emerging evidence highlights region-specific astrocyte subtypes whose distinct gene-expression profiles influence disease onset and progression. Understanding the dual roles of astrocytes in neuroprotection and neurotoxicity is critical for the development of targeted therapies that modulate glial function without undermining their supportive capacity.

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Astrocytic Interactions in Neurodegenerative Disease Pathogenesis publication trend

The graph below shows the total number of articles in astrocytic interactions in neurodegenerative disease pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Astrocyte: Star-shaped glial cell involved in metabolic support, neurotransmitter recycling and blood–brain barrier maintenance.

Reactive astrogliosis: Phenotypic transformation of astrocytes in response to injury, characterised by hypertrophy, gene-expression changes and altered cytokine release.

Autophagy: Intracellular degradation pathway that delivers misfolded proteins and damaged organelles to lysosomes for recycling.

α-Synuclein: Neuronal protein prone to misfolding and aggregation in Parkinson’s disease and related synucleinopathies.

Neuroinflammation: Localised inflammatory response within the central nervous system driven by glial activation and cytokine production.

References

1. Brain clearance of protein aggregates: a close-up on astrocytes. Molecular Neurodegeneration (2024).
2. Astrocytes contribute to toll-like receptor 2-mediated neurodegeneration and alpha-synuclein pathology in a human midbrain Parkinson’s model. Translational Neurodegeneration (2024).
3. RGS5 augments astrocyte activation and facilitates neuroinflammation via TNF signaling. Journal of Neuroinflammation (2023).