title: RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis.
abstract: 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.
authors.affiliation: Qilu Hospital of Shandong University, Jinan, China; Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, Graduate Program in Neuroscience, The University of British Columbia, Vancouver, Canada.
authors.forename: Xiulian
authors.initials: X
authors.lastname: Sun
authors.affiliation: Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, Graduate Program in Neuroscience, The University of British Columbia, Vancouver, Canada.
authors.forename: Yili
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, Graduate Program in Neuroscience, The University of British Columbia, Vancouver, Canada.
authors.forename: Bruno
authors.initials: B
authors.lastname: Herculano
authors.affiliation: Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, Graduate Program in Neuroscience, The University of British Columbia, Vancouver, Canada.
authors.forename: Weihong
authors.initials: W
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; D009498:Neurotoxins; D020033:Protein Isoforms; C108612:RCAN1 protein, human; D053148:Caspase 3; D002118:Calcium
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