Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration

Targeting disease-defining markers in conditions such as Alzheimer's disease (amyloid-β and tau) or Parkinson's disease (α-synuclein) has been met with limited success, suggesting that these proteins do not act in isolation but form part of a pathological network. Transcriptomic studies in human patients and disease models have revealed the co-existence of many putative reactive sub-states of astrocytes. This review highlights how single-cell and single-nuclei RNA sequencing and other ‘omics’ technologies can enable the functional characterization of defined reactive astrocyte states in various pathological scenarios. This review provides an integrated perspective, advocating cross-modal validation of key findings to define functionally important sub-states of astrocytes and their triggers as tractable therapeutic targets with cross-disease relevance.