Astrocytes, an active player in Aicardi–Goutières syndrome

Sunetra Sase, Asako Takanohashi, Adeline Vanderver, Akshata Almad

Research output: Contribution to journalArticle

Abstract

Aicardi–Goutières syndrome (AGS) is an early-onset, autoimmune and genetically heterogeneous disorder with severe neurologic injury. Molecular studies have established that autosomal recessive mutations in one of the following genes are causative: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 and IFIH1/MDA5. The phenotypic presentation and pathophysiology of AGS is associated with over-production of the cytokine Interferon–alpha (IFN-α) 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-brain barrier, maintaining ionic homeostasis, metabolic support to synapse formation and elimination in healthy CNS. Involvement of astrocytic dysfunction in neurological diseases—Alexander's disease, Epilepsy, Alzheimer's and amyotrophic lateral sclerosis (ALS)—has been well-established. 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-α signaling. We shed light on how astrocytes might be key players in the phenotypic presentations of AGS and emphasize the cell-autonomous and non-cell-autonomous role of astrocytes. Understanding the contribution of astrocytes will help reveal mechanisms underlying interferonopathy and develop targeted astrocyte specific therapeutic treatments in AGS.

Original languageEnglish (US)
Pages (from-to)399-407
Number of pages9
JournalBrain Pathology
Volume28
Issue number3
DOIs
StatePublished - May 1 2018
Externally publishedYes

Fingerprint

Astrocytes
Central Nervous System
Nervous System Malformations
Nervous System Trauma
Mutation
Amyotrophic Lateral Sclerosis
Blood-Brain Barrier
Neuroglia
Synapses
Epilepsy
Alzheimer Disease
Homeostasis
Pathology
Cytokines
Therapeutics
Genes

Keywords

  • Aicardi–Goutières syndrome
  • astrocytes
  • interferon
  • type I interferonopathy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Sase, S., Takanohashi, A., Vanderver, A., & Almad, A. (2018). Astrocytes, an active player in Aicardi–Goutières syndrome. Brain Pathology, 28(3), 399-407. https://doi.org/10.1111/bpa.12600

Astrocytes, an active player in Aicardi–Goutières syndrome. / Sase, Sunetra; Takanohashi, Asako; Vanderver, Adeline; Almad, Akshata.

In: Brain Pathology, Vol. 28, No. 3, 01.05.2018, p. 399-407.

Research output: Contribution to journalArticle

Sase, S, Takanohashi, A, Vanderver, A & Almad, A 2018, 'Astrocytes, an active player in Aicardi–Goutières syndrome', Brain Pathology, vol. 28, no. 3, pp. 399-407. https://doi.org/10.1111/bpa.12600
Sase S, Takanohashi A, Vanderver A, Almad A. Astrocytes, an active player in Aicardi–Goutières syndrome. Brain Pathology. 2018 May 1;28(3):399-407. https://doi.org/10.1111/bpa.12600
Sase, Sunetra ; Takanohashi, Asako ; Vanderver, Adeline ; Almad, Akshata. / Astrocytes, an active player in Aicardi–Goutières syndrome. In: Brain Pathology. 2018 ; Vol. 28, No. 3. pp. 399-407.
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