RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis
Down Syndrome (DS) patients develop characteristic Alzheimer's Disease (AD) neuropathology after their middle age. Prominent neuronal loss has been observed in the cortical regions of AD brains. However, the underlying mechanism leading to this neuronal loss in both DS and AD remains to be eluc...
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Published in | PloS one Vol. 9; no. 4; p. e95471 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
01.04.2014
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | Down Syndrome (DS) patients develop characteristic Alzheimer's Disease (AD) neuropathology after their middle age. Prominent neuronal loss has been observed in the cortical regions of AD brains. However, the underlying mechanism leading to this neuronal loss in both DS and AD remains to be elucidated. Calcium overloading and oxidative stress have been implicated in AD pathogenesis. Two major isoforms of regulator of calcineurin 1 (RCAN1), RCAN1.1 and RCAN1.4, are detected in human brains. In this report we defined the transcriptional regulation of RCAN1.1 and RCAN1.4 by two alternative promoters. Calcium overloading upregulated RCAN1.4 expression by activating RCAN1.4 promoter through calcineurin-NFAT signaling pathway, thus forming a negative feedback loop in isoform 4 regulation. Furthermore, RCAN1.4 overexpression exacerbated calcium overloading-induced neuronal apoptosis, which was mediated by caspase-3 apoptotic pathway. Our results suggest that downregulating RCAN1.4 expression in neurons could be beneficial to AD patients. |
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Bibliography: | Conceived and designed the experiments: XS YW WS. Performed the experiments: XS YW BH. Analyzed the data: XS YW WS. Contributed reagents/materials/analysis tools: XS WS. Wrote the paper: XS YW WS. Competing Interests: The authors have declared that no competing interests exist. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0095471 |