Regulation of Extrasynaptic Glutamatergic Signaling by Polysialylated NCAM in Health and Disease

Cells 2023 Pub Date : 2023-04-03 DOI:10.3390/blsf2023021030
A. Dityatev
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引用次数: 0

Abstract

: The neural cell adhesion molecule NCAM is known to mediate cell–to–cell and cell–to– extracellular matrix (ECM) adhesion via homophilic and heterophilic interactions. During brain development, NCAM and the associated glycan, polysialic acid (polySia), play important roles in cell migration proliferation, neurite outgrowth and fasciculation, and synaptogenesis. In the adult rodent brain, NCAM regulates synaptic plasticity, learning, and memory. Dysregulated cortical expression of NCAM and polySia has been reported in Alzheimer’s disease and schizophrenia. Our data demonstrate i) the importance of polySia–NCAM in the balancing of signaling through synaptic/extrasynaptic NMDA receptors and ii) the therapeutic value of short defined-length polySia fragments to restrain GluN2B-mediated signaling in several animal models of neurological and psychiatric diseases.
多唾液化的NCAM在健康和疾病中调节突触外谷氨酸能信号
神经细胞粘附分子NCAM通过嗜同性和嗜异性相互作用介导细胞间和细胞外基质(ECM)的粘附。在大脑发育过程中,NCAM及其相关聚糖聚唾液酸(polySia)在细胞迁移、增殖、神经突生长和束状形成以及突触发生中发挥重要作用。在成年啮齿动物的大脑中,NCAM调节突触可塑性、学习和记忆。在阿尔茨海默病和精神分裂症中已经报道了NCAM和polySia皮层表达失调。我们的数据证明了i) polySia - ncam在通过突触/突触外NMDA受体的信号平衡中的重要性,ii)在几种神经和精神疾病的动物模型中,短定义长度的polySia片段抑制glun2b介导的信号传导的治疗价值。
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