Abstract
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.
Document Type
Review
Publication Date
7-9-2018
Digital Object Identifier (DOI)
https://doi.org/10.3389/fnagi.2018.00199
Funding Information
This work was supported by National Institutes of Health Grants AG027297, AG051945 and AG056998 and a gift from the Hazel Embry Research Trust.
Repository Citation
Sompol, Pradoldej and Norris, Christopher M., "Ca2+, Astrocyte Activation and Calcineurin/NFAT Signaling in Age-Related Neurodegenerative Diseases" (2018). Sanders-Brown Center on Aging Faculty Publications. 115.
https://uknowledge.uky.edu/sbcoa_facpub/115
Included in
Cognitive Neuroscience Commons, Diseases Commons, Geriatrics Commons, Neurology Commons, Neurosciences Commons
Notes/Citation Information
Published in Frontiers in Aging Neuroscience, v. 10, 199, p. 1-14.
© 2018 Sompol and Norris.
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