Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center, Room 610, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Sci Signal. 2010 Jun 8;3(125):pe20. doi: 10.1126/scisignal.3125pe20.
Ischemic tolerance is an evolutionarily conserved form of cerebral plasticity in which a brief period of cerebral ischemia (called ischemic preconditioning) confers transient tolerance to a subsequent ischemic challenge in the brain. Polycomb group proteins are gene-silencing factors that are abundant and widely distributed during embryogenesis and are essential to epigenetic cellular memory, pluripotency, and stem cell self-renewal. New insight into the molecular mechanisms underlying ischemic tolerance is highlighted by the finding that ischemic preconditioning activates polycomb proteins in mature neurons. Polycomb proteins act through epigenetic gene silencing to eradicate potential mediators of neuronal death and promote cellular arrest, enabling mature neurons to survive ischemic stroke.
缺血耐受是大脑可塑性的一种进化保守形式,其中短暂的脑缺血(称为缺血预处理)赋予大脑随后的缺血性挑战短暂的耐受性。多梳组蛋白是基因沉默因子,在胚胎发生期间丰富且广泛分布,对表观遗传细胞记忆、多能性和干细胞自我更新至关重要。缺血预处理激活成熟神经元中的多梳蛋白这一发现突出了对缺血耐受相关分子机制的新认识。多梳蛋白通过表观遗传基因沉默来消除神经元死亡的潜在介质,并促进细胞停滞,使成熟神经元能够在缺血性中风中存活。