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Neurodegenerative disease

Remodelling neurodegeneration

Nature Reviews Neuroscience volume 19, page 3 (2018)Cite this article

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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.

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References

  1. 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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  1. Sian Lewis
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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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