Interaction of nNOS with PSD-95 Negatively Controls Regenerative Repair after Stroke
Interaction of nNOS with PSD-95 Negatively Controls Regenerative Repair after Stroke
复制标题
nNOS 与 PSD-95 的相互作用负向控制中风后的再生修复。
DOI：
10.1523/jneurosci.1305-14.2014
复制
发表时间：
2014-10-01
影响因子：
5.3
通讯作者：
Zhu, Dong-Ya
中科院分区：
文献类型：
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作者：
Luo, Chun-Xia;Lin, Yu-Hui;Zhu, Dong-Ya
中风是一个主要的公共卫生问题。缺乏有效的治疗方法增加了对新的治疗靶点的需求。哺乳动物的大脑有自我重组的能力来恢复失去的功能。促进再生修复，包括神经发生和树突重塑，可能为治疗中风提供一种新的治疗策略。在这里，我们报道了神经元一氧化氮合酶（nNOS）与突触后密度-95蛋白（PSD-95）的相互作用对大鼠中风后的再生修复产生负性控制。神经元中分离的nNOS-PSD-95偶联可促进神经干细胞（NSCs）的神经元分化，促进新生细胞向损伤区迁移，促进新生神经元的神经突生长和成熟神经元树突棘的形成。更重要的是，在恢复阶段阻断nNOS-PSD-95的结合，通过促进大鼠的再生修复来改善中风结果。NSCs中的组蛋白去乙酰化酶2可能介导nNOS-PSD-95关联的作用。因此，nNOS-PSD-95可以作为脑卒中后再生修复的靶点。
Stroke is a major public health concern. The lack of effective therapies heightens the need for new therapeutic targets. Mammalian brain has the ability to rewire itself to restore lost functionalities. Promoting regenerative repair, including neurogenesis and dendritic remodeling, may offer a new therapeutic strategy for the treatment of stroke. Here, we report that interaction of neuronal nitric oxide synthase (nNOS) with the protein postsynaptic density-95 (PSD-95) negatively controls regenerative repair after stroke in rats. Dissociating nNOS-PSD-95 coupling in neurons promotes neuronal differentiation of neural stem cells (NSCs), facilitates the migration of newborn cells into the injured area, and enhances neurite growth of newborn neurons and dendritic spine formation of mature neurons in the ischemic brain of rats. More importantly, blocking nNOS-PSD-95 binding during the recovery stage improves stroke outcome via the promotion of regenerative repair in rats. Histone deacetylase 2 in NSCs may mediate the role of nNOS-PSD-95 association. Thus, nNOS-PSD-95 can serve as a target for regenerative repair after stroke.