Berezin Vladimir, Bock Elisabeth
Protein Laboratory, Institute of Molecular Pathology, University of Copenhagen, Panum Institute 6.2, Blegdamsvej 3, DK-2200 Copenhagen N., Denmark.
J Mol Neurosci. 2004;22(1-2):33-39. doi: 10.1385/JMN:22:1-2:33.
The neural cell adhesion molecule (NCAM) plays an important role in neuronal differentiation and synaptic plasticity, making it an attractive target for the development of drugs for the treatment of neurodegenerative disorders. NCAM binds to itself (homophilic binding) and to a series of counter-receptors, including the fibroblast growth factor receptor (FGFR), other adhesion molecules, and various extracellular matrix components (heterophilic binding). By means of combinatorial chemistry and based on the unraveling of the structure of NCAM, it has been possible to develop a number of peptides that mimic NCAM homophilic binding. These peptides interfere with cell adhesion and promote differentiation and cell survival. Recently, a peptide mimicking the heterophilic binding to FGFR has also been identified. It binds and activates the receptor, thereby modulating neurite extension and synaptic plasticity.
神经细胞黏附分子（NCAM）在神经元分化和突触可塑性中发挥着重要作用，这使其成为开发治疗神经退行性疾病药物的一个有吸引力的靶点。NCAM能与自身结合（同源性结合），还能与一系列反受体结合，包括成纤维细胞生长因子受体（FGFR）、其他黏附分子以及各种细胞外基质成分（异源性结合）。通过组合化学并基于对NCAM结构的解析，已经能够开发出一些模拟NCAM同源性结合的肽。这些肽会干扰细胞黏附，并促进分化和细胞存活。最近，还鉴定出了一种模拟与FGFR异源性结合的肽。它能结合并激活受体，从而调节神经突延伸和突触可塑性。
