Astrocytes are abundant glial cells in the central nervous system (CNS) that perform diverse functions in health and disease. Astrocyte dysfunction is found in numerous diseases, including multiple sclerosis, Alzheimer disease, Parkinson disease, Huntington disease and neuropsychiatric disorders. Astrocytes regulate glutamate and ion homeostasis, cholesterol and sphingolipid metabolism and respond to environmental factors, all of which have been implicated in neurological diseases. Astrocytes also exhibit significant heterogeneity, driven by developmental programmes and stimulus-specific cellular responses controlled by CNS location, cell-cell interactions and other mechanisms. In this Review, we highlight general mechanisms of astrocyte regulation and their potential as therapeutic targets, including drugs that alter astrocyte metabolism, and therapies that target transporters and receptors on astrocytes. Emerging ideas, such as engineered probiotics and glia-to-neuron conversion therapies, are also discussed. We further propose a concise nomenclature for astrocyte subsets that we use to highlight the roles of astrocytes and specific subsets in neurological diseases.

Increased awareness of autoimmune encephalitis has led to two unintended consequences: a high frequency of misdiagnoses and the inappropriate use of diagnostic criteria for antibody-negative disease. Misdiagnoses typically occur for three reasons: first, non-adherence to reported clinical requirements for considering a disorder as possible autoimmune encephalitis; second, inadequate assessment of inflammatory changes in brain MRI and CSF; and third, absent or limited use of brain tissue assays along with use of cell-based assays that include only a narrow range of antigens. For diagnosis of possible autoimmune encephalitis and probable antibody-negative autoimmune encephalitis, clinicians should adhere to published criteria for adults and children, focusing particularly on exclusion of alternative disorders. Moreover, for diagnosis of probable antibody-negative autoimmune encephalitis, the absence of neural antibodies in CSF and serum should be well substantiated. Neural antibody testing should use tissue assays along with cell-based assays that include a broad range of antigens. Live neuronal studies in specialised centres can assist in resolving inconsistencies with respect to syndrome-antibody associations. Accurate diagnosis of probable antibody-negative autoimmune encephalitis will identify patients with similar syndromes and biomarkers, which will provide homogeneous populations for future assessments of treatment response and outcome.