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- W2061466239 abstract "Amyloid β (Aβ) peptides, the main pathological species associated with Alzheimer's disease (AD), disturb intracellular calcium homeostasis, which in turn activates the calcium-dependent phosphatase calcineurin (CaN). CaN activation induced by Aβ leads to pathological morphological changes in neurons, and overexpression of constitutively active calcineurin is sufficient to generate a similar phenotype, even without Aβ. Here, we tested the hypothesis that calcineurin mediates neurodegenerative effects via activation of the nuclear transcription factor of activated T-cells (NFAT). We found that both spine loss and dendritic branching simplification induced by Aβ exposure were mimicked by constitutively active NFAT, and abolished when NFAT activation was blocked using the genetically encoded inhibitor VIVIT. When VIVIT was specifically addressed to the nucleus, identical beneficial effects were observed, thus enforcing the role of NFAT transcriptional activity in Aβ-related neurotoxicity. In vivo, when VIVIT or its nuclear counterpart were overexpressed in a transgenic model of Alzheimer's disease via a gene therapy approach, the spine loss and neuritic abnormalities observed in the vicinity of amyloid plaques were blocked. Overall, these results suggest that NFAT/calcineurin transcriptional cascades contribute to Aβ synaptotoxicity, and may provide a new specific set of pathways for neuroprotective strategies." @default.
- W2061466239 created "2016-06-24" @default.
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- W2061466239 date "2012-02-29" @default.
- W2061466239 modified "2023-09-29" @default.
- W2061466239 title "Inhibition of the NFAT Pathway Alleviates Amyloid Beta Neurotoxicity in a Mouse Model of Alzheimer's Disease" @default.
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- W2061466239 cites W1525008978 @default.
- W2061466239 cites W1569503463 @default.
- W2061466239 cites W1972797480 @default.
- W2061466239 cites W1975371118 @default.
- W2061466239 cites W1980830385 @default.
- W2061466239 cites W1984009511 @default.
- W2061466239 cites W1984899161 @default.
- W2061466239 cites W1984924722 @default.
- W2061466239 cites W1985241009 @default.
- W2061466239 cites W1987269633 @default.
- W2061466239 cites W1988278010 @default.
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- W2061466239 cites W1990233366 @default.
- W2061466239 cites W1990752558 @default.
- W2061466239 cites W1991797169 @default.
- W2061466239 cites W1993124121 @default.
- W2061466239 cites W1995839809 @default.
- W2061466239 cites W1997102660 @default.
- W2061466239 cites W1997301424 @default.
- W2061466239 cites W2000129128 @default.
- W2061466239 cites W2003493421 @default.
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- W2061466239 cites W2013224564 @default.
- W2061466239 cites W2014530155 @default.
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- W2061466239 cites W2023200476 @default.
- W2061466239 cites W2028211858 @default.
- W2061466239 cites W2029904277 @default.
- W2061466239 cites W2033606638 @default.
- W2061466239 cites W2035302673 @default.
- W2061466239 cites W2048685634 @default.
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- W2061466239 cites W2075481535 @default.
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- W2061466239 doi "https://doi.org/10.1523/jneurosci.6439-11.2012" @default.
- W2061466239 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3296329" @default.
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