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

摘要

Transient forebrain or global ischemia arising during cardiac arrest affects 200,000 Americans each year and in many cases, results in the delayed death of hippocampal neurons critical to memory formation and retrieval. Neurological sequelae include deficits in learning and memory. The substantial delay between insult and cell death is consistent with a role for changes in gene expression. Repressor ele-ment-1 silencing transcription factor (REST)euron-re-strictive silencing factor (NRSF) is a DNA binding protein that is widely expressed during em-bryogenesis and vital for the transition from pluripotent stem cells to mature neurons (1, 2). In pluripotent stem cells and neural progenitor cells, REST actively represses a large array of neuron-specific genes important for synaptic plasticity, the phenomenon whereby the connection between two neurons (synapses) change in strength and is structurally remodeled (1, 2). A prevailing view is that,