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PLoS One. 2012;7(9):e44099. doi: 10.1371/journal.pone.0044099. Epub 2012 Sep 5.

Transposable elements in TDP-43-mediated neurodegenerative disorders.

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Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, New York, United States of America.


Elevated expression of specific transposable elements (TEs) has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases.

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