Mounting evidence supports a fundamental role for Ca2+ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca2+/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca2+ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and vascular pathology. Similar upregulation of the CN-dependent transcription factor nuclear factor of activated T cells (NFAT4) also appears in activated astrocytes in mouse models of Alzheimer's disease (ADs) and traumatic brain injury (TBI). Major consequences of hyperactivated CN/NFAT4 signaling in astrocytes are neuroinflammation, synapse dysfunction and glutamate dysregulation/excitotoxicity, which will be covered in this review article.
|Journal||Frontiers in Aging Neuroscience|
|State||Published - Jul 9 2018|
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health Grants AG027297, AG051945 and AG056998 and a gift from the Hazel Embry Research Trust.
© 2018 Sompol and Norris.
- Alzheimer's disease
ASJC Scopus subject areas
- Cognitive Neuroscience