TAR DNA-binding protein 43 (TDP43) is implicated in amyotrophic lateral sclerosis (ALS) and in some cases of frontotemporal dementia (FTD). Here, in a fly model of ALS–FTD, TDP43 reduced the recruitment of chromodomain-helicase-DNA-binding protein 1 (Chd1), a chromatin remodelling protein, to neuroprotective stress genes, resulting in reduced gene expression. TDP43 interacted directly with CHD2 (the human orthologue of Chd1), which is found at a reduced level in the cortex of individuals with FTD. This suggests that enhancing chromatin dynamics at stress genes might mitigate the effects of TDP43 in these disorders.
References
Berson, A. et al. TDP-43 promotes neurodegeneration by impairing chromatin remodeling. Curr. Biol. http://dx.doi.org/10.1016/j.cub.2017.10.024 (2017)
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Lewis, S. Remodelling neurodegeneration. Nat Rev Neurosci 19, 3 (2018). https://doi.org/10.1038/nrn.2017.152
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DOI: https://doi.org/10.1038/nrn.2017.152