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P4‐066: Disrupted nuclear transport: A central event in Alzheimer's pathophysiology
Author(s) -
Mastroeni Diego,
Hauns Kevin,
Grover Andrew,
Rogers Joseph,
Coleman Paul D.
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1768
Subject(s) - cytoplasm , transcription factor , epigenetics , transcription (linguistics) , microbiology and biotechnology , nucleus , cell nucleus , biology , in situ hybridization , nuclear protein , nuclear localization sequence , in vitro , dna , gene expression , gene , genetics , linguistics , philosophy
Background: Transcription of DNA is regulated by the actions of several classes of proteins on nuclear DNA. Epigenetic molecules are central to this process.Methods:We used immunohistochemistry, in situ hybridization, Western blotting, siRNA and in vitro methods in human, t.g. mice and cell lines to examine cellular localization and expression of epigentic molecules. Results: Alzheimer’s disease results in inability of transcription regulatory molecules to access neuronal nuclei, with an accompanying build up of these molecules in the cytoplasm. These effects involve altered expression of RAN andmay be driven by specific forms of Abeta.Conclusions:Our data suggest a model in which failed localization of transcription regulatory molecules to the cell nucleus can have dramatic effects on transcription.