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Molecular studies have established that autosomal recessive mutations in one of the following genes are causative: <jats:italic>TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1<\/jats:italic> and <jats:italic>IFIH1\/MDA5<\/jats:italic>. The phenotypic presentation and pathophysiology of AGS is associated with over\u2010production of the cytokine Interferon\u2013alpha (IFN\u2010\u03b1) and its downstream signaling, characterized as type I interferonopathy. Astrocytes are one of the major source of IFN in the central nervous system (CNS) and it is proposed that they could be key players in AGS pathology. Astrocytes are the most ubiquitous glial cell in the CNS and perform a number of crucial and complex functions ranging from formation of blood\u2010brain barrier, maintaining ionic homeostasis, metabolic support to synapse formation and elimination in healthy CNS. Involvement of astrocytic dysfunction in neurological diseases\u2014Alexander's disease, Epilepsy, Alzheimer's and amyotrophic lateral sclerosis (ALS)\u2014has been well\u2010established. It is now known that compromised astrocytic function can contribute to CNS abnormalities and severe neurodegeneration, nevertheless, its contribution in AGS is unclear. The current review discusses known molecular and cellular pathways for AGS mutations and how it stimulates IFN\u2010\u03b1 signaling. We shed light on how astrocytes might be key players in the phenotypic presentations of AGS and emphasize the cell\u2010autonomous and non\u2010cell\u2010autonomous role of astrocytes. Understanding the contribution of astrocytes will help reveal mechanisms underlying interferonopathy and develop targeted astrocyte specific therapeutic treatments in AGS.<\/jats:p>","DOI":"10.1111\/bpa.12600","type":"journal-article","created":{"date-parts":[[2018,5,9]],"date-time":"2018-05-09T04:48:18Z","timestamp":1525841298000},"page":"399-407","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Astrocytes, an active player in Aicardi\u2013Gouti\u00e8res syndrome"],"prefix":"10.1111","volume":"28","author":[{"given":"Sunetra","family":"Sase","sequence":"first","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia Philadelphia PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asako","family":"Takanohashi","sequence":"additional","affiliation":[{"name":"Division of Neurology Children's Hospital of Philadelphia Philadelphia 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