Repressor element-1 silencing transcription factor (REST)-dependent epigenetic remodeling is critical to ischemia-induced neuronal death

I got nothing out of this so your doctor can contact the two given email addresses to see what needs to be done to followup research in humans and create a stroke protocol for this. No followup, they need to be fired. Dead wood needs to be removed. 
http://www.pnas.org/content/early/2012/02/24/1121568109.short

Kyung-Min Noh, Jee-Yeon Hwang, Antonia Follenzi, Rodoniki Athanasiadou, Takahiro Miyawaki, John M. Greally, Michael V. L. Bennett, and R. Suzanne Zukin

PNAS February 27, 2012. 201121568; published ahead of print February 27, 2012. https://doi.org/10.1073/pnas.1121568109

1. Contributed by Michael V. L. Bennett, January 15, 2012 (sent for review December 22, 2011)

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Abstract

Dysregulation of the transcriptional repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor is important in a broad range of diseases, including cancer, diabetes, and heart disease. The role of REST-dependent epigenetic modifications in neurodegeneration is less clear. Here, we show that neuronal insults trigger activation of REST and CoREST in a clinically relevant model of ischemic stroke and that REST binds a subset of “transcriptionally responsive” genes (gria2, grin1, chrnb2, nefh, nfκb2, trpv1, chrm4, and syt6), of which the AMPA receptor subunit GluA2 is a top hit. Genes with enriched REST exhibited decreased mRNA and protein. We further show that REST assembles with CoREST, mSin3A, histone deacetylases 1 and 2, histone methyl-transferase G9a, and methyl CpG binding protein 2 at the promoters of target genes, where it orchestrates epigenetic remodeling and gene silencing. RNAi-mediated depletion of REST or administration of dominant-negative REST delivered directly into the hippocampus in vivo prevents epigenetic modifications, restores gene expression, and rescues hippocampal neurons. These findings document a causal role for REST-dependent epigenetic remodeling in the neurodegeneration associated with ischemic stroke and identify unique therapeutic targets for the amelioration of hippocampal injury and cognitive deficits.

• chromatin remodeling
• global ischemia
• CA1
• synaptic plasticity

Footnotes

• ↵¹K.-M.N. and J.-Y.H. contributed equally to this work.
• ↵²To whom correspondence may be addressed. E-mail: michael.bennett@einstein.yu.edu or suzanne.zukin@einstein.yu.edu.