Notch: from neural development to neurological disorders.
Notch: from neural development to neurological disorders.
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DOI：
10.1111/j.1471-4159.2008.05715.x
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发表时间：
2008-12
影响因子：
4.7
通讯作者：
Cheng A
中科院分区：
文献类型：
--
作者：
Lathia JD;Mattson MP;Cheng A
Noch是一种完整的膜蛋白，其功能是作为与相邻细胞表面相关的配体的受体，如锯齿状和Delta。当与配体结合时，Noch在其跨膜区内被早老素-1(γ-分泌酶复合体的酶组分)蛋白水解性切割，导致Notch胞内域的释放，该区域移位到细胞核，在那里它调节基因的表达。Notch信号在中枢神经系统(CNS)的发育过程中发挥着多种作用，包括调节神经干细胞(NSC)的增殖、存活、自我更新和分化。Notch也存在于成年中枢神经系统的有丝分裂后神经元中，它的激活影响结构和功能的可塑性，包括参与学习和记忆的过程。最近的发现表明，神经元、神经胶质细胞和神经干细胞中的Notch信号可能参与了中风、阿尔茨海默病和中枢神经系统肿瘤等疾病的病理变化。对动物模型的研究表明，靶向缺口信号的药物有可能作为几种不同中枢神经系统疾病的治疗干预措施。
Notch is an integral membrane protein that functions as receptor for ligands such as jagged and delta that are associated with the surface of neighboring cells. Upon ligand binding, notch is proteolytically cleaved within its transmembrane domain by presenilin-1 (the enzymatic component of the γ-secretase complex) resulting in the release of a notch intracellular domain (NICD) which translocates to the nucleus where it regulates gene expression. Notch signaling plays multiple roles in the development of the central nervous system (CNS) including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation. Notch is also present in postmitotic neurons in the adult CNS wherein its activation influences structural and functional plasticity including processes involved in learning and memory. Recent findings suggest that notch signaling in neurons, glia and NSCs may be involved in pathological changes that occur in disorders such as stroke, Alzheimer’s disease and CNS tumors. Studies of animal models suggest the potential of agents that target notch signaling as therapeutic interventions for several different CNS disorders.