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RCAN1‐1L is overexpressed in neurons of Alzheimer's disease patients
Author(s) -
Harris Cathryn D.,
Ermak Gennady,
Davies Kelvin J. A.
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05717.x
Subject(s) - gene isoform , exon , human brain , biology , microglia , in situ hybridization , blot , alzheimer's disease , messenger rna , immunohistochemistry , disease , microbiology and biotechnology , pathology , gene , neuroscience , medicine , genetics , immunology , inflammation
At least two different isoforms of RCAN1 mRNA are expressed in neuronal cells in normal human brain. Although RCAN1 mRNA is elevated in brain regions affected by Alzheimer's disease, it is not known whether the disease affects neuronal RCAN1, or if other cell types (e.g. astrocytes or microglia) are affected. It is also unknown how many protein isoforms are expressed in human brain and whether RCAN1 protein is overexpressed in Alzheimer's disease. We explored the expression of both RCAN1‐1 and RCAN1‐4 mRNA isoforms in various cell types in normal and Alzheimer's disease postmortem samples, using the combined technique of immunohistochemistry and in situ hybridization. We found that both exon 1 and exon 4 are predominantly expressed in neuronal cells, and no significant expression of either of the exons was observed in astocytes or microglial cells. This was true in both normal and Alzheimer's disease brain sections. We also demonstrate that RCAN1‐1 mRNA levels are approximately two‐fold higher in neurons from Alzheimer's disease patients versus non‐Alzheimer's disease controls. Using western blotting, we now show that there are three RCAN1 protein isoforms expressed in human brain: RCAN1‐1L, RCAN1‐1S, and RCAN1‐4. We have determined that RCAN1‐1L is expressed at twice the level of RCAN1‐4, and that there is very minor expression of RCAN1‐1S. We also found that the RCAN1‐1L protein is overexpressed in Alzheimer's disease patients, whereas RCAN1‐4 is not. From these results, we conclude that RCAN1‐1 may play a role in Alzheimer's disease, whereas RCAN1‐4 may serve another purpose.