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Roles of neuropathology-associated reactive astrocytes: a systematic review

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BMC
DOI: 10.1186/s40478-023-01526-9

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Neurotoxic reactive astrocytes; Activated astrocytes; A1 astrocytes; Neuroinflammation; Neurodegeneration

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In the contexts of aging, injury, or neuroinflammation, activated microglia induce neurotoxic astrocytes that downregulate supportive functions and secrete neurotoxic factors, complement components, and chemokines, which may facilitate immune cell recruitment. The proportion of pro-inflammatory reactive astrocytes increases with age and is particularly abundant in neurodegenerative disorders. As the identification of astrocyte phenotypes progress, their molecular and cellular effects are characterized in a growing array of neuropathologies.
In the contexts of aging, injury, or neuroinflammation, activated microglia signaling with TNF-alpha, IL-1 alpha, and C1q induces a neurotoxic astrocytic phenotype, classified as A1, A1-like, or neuroinflammatory reactive astrocytes. In contrast to typical astrocytes, which promote neuronal survival, support synapses, and maintain blood-brain barrier integrity, these reactive astrocytes downregulate supportive functions and begin to secrete neurotoxic factors, complement components like C3, and chemokines like CXCL10, which may facilitate recruitment of immune cells across the BBB into the CNS. The proportion of pro-inflammatory reactive astrocytes increases with age through associated microglia activation, and these pro-inflammatory reactive astrocytes are particularly abundant in neurodegenerative disorders. As the identification of astrocyte phenotypes progress, their molecular and cellular effects are characterized in a growing array of neuropathologies.

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