2.4 NCAM和临床眼科疾病 粘附分子和眼科疾病的关系研究才刚刚起步,如羊膜移植可通过降低角膜组织细胞间粘附分子-1(ICAM-1)的表达水平来抑制炎症反应[28]。而NCAM在眼科疾病中的研究更少,以前有学者认为免疫球蛋白超家族如NCAM等在神经肿瘤细胞上不同的表达量代表着肿瘤细胞不同的分化阶段。近年来有学者[29]研究免疫球蛋白超家族在原发性视网膜母细胞瘤的表达中发现,其瘤细胞出现高水平的NCAM免疫反应性。研究发现,NCAM和其他粘附分子的调节与肿瘤细胞局部的浸润转移有关[30],非唾液酸化的NCAM表达的减少,降低了细胞的粘附作用,从而有助于肿瘤细胞的转移[31]。 综上所述,尽管NCAM的结构及其在神经系统中的作用已取得了一些研究成果,但在其作用机制方面尚存争议。例如,NCAM的5个Ig组件在反式作用中所扮演的角色问题,不同的学者观点不一,尚缺乏确凿的实验数据加以证实[32-34]。目前NCAM在眼科学领域中的研究多局限于离体研究,很少对NCAM分子进行活体研究;NCAM和视网膜母细胞瘤的关系尚未明了,NCAM表达对视网膜母细胞瘤的生长会产生何种影响,NCAM对视神经的发育及再生等的影响机理还不清楚,这些问题均有待于进一步的研究和探索。
参考文献: [1]Kiselyov VV,Skladchikova G,Hinsby AM,Jensen PH,Kulahin N,Soroka V,Pedersen N,Tsetlin V,Poulsen FM,Berezin V,Bock E.Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP.Structure,2003; 11 (6):691-701 [2]Nakayama J,Angata K,Ong E,Katsuyama T,Fukuda M.Polysialic aeid,a unique glycan that is developmentally regulated by two polysialyltransferases,PST and STX,in the central nervous system:from biosynthesis to function.Pathol Int,1998;48(9):665-677 [3]Rutisbauser U,Landmesser L.Polysialic acid in the vertebrate nervoussystem:a promoter of plasticityin cell-cell interactions.Trends Neurosci,1996; 19 (10):422-427 [4]Bruses JL,Rutishauser U.Roles,regulation,and mechanism of polysialic acid function during neural development.Biochimie,2001;83(7):635-643 [5]Polo-Parada L,Bose CM,Plattner F,Landmesser LT.Distinct roles of different neural cell adhesion molecule (NCAM) isoforms in synaptic maturation revealed by analysis of NCAM 180 kDa isoform-deficient mice.J Neurosci,2004;24(8):1852-1864 [6]Kiselyov VV,Soroka V,Berezin V,Bock E.Structural biology of NCAM homophilic binding and activation of FGFR.J Neurochem,2005;94 (5):1169-1179 [7]Johnson CP,Fujimoto I,Rutishauser U,Leckband DE.Direct evidence that neural cel1 adhesion molecule (NCAM) polysialylation increases intermembrane repulsion and abrogates adhesion.J Biol Chem,2005;280(1):137-145 [8]S(o)ren P,Eugene AL,Kateryna K,Rasmus HP,Anna K,Peter SW,Vadym B,Helen CG,Vladimir B,Elisabeth B,Nina P.NCAM regulates cell motility.J Cell Sci,2002; 115:283-292 [9]Cremer H,Chazal G,Carleton A,Goridis C,Vincent JD,Lledo PM.Long-term but not short-term plasticity at mossy fiber synapses is impaired in neural cell adhesion molecule-deficient mice.Proc Natl Acad Sci USA,1998;95(13):242-247 [10]Seidenfaden R,Krauter A,Schertzinger F,Gerardy-Schahn R,Hildebrandt H.Polysialic acid directs tumor cell growth by controlling heterophilic neural cell adhesion molecule interactions.Mol Cell Biol,2003;23 (16):5908-5918 [11]Cambon K,Hansen SM,Venero C,Herrero AI,Skibo G,Berezin V,Bock E,Sandi C.A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis,enhances presynaptic function,and facilitates memory consolidation.J Neurosci,2004;24(17):4197-4204 [12]Venero C,Herrero AI,Touyarot K,Cambon K,López-Fernández MA,Berezin V,Bock E,Sandi C.Hippocampal up-regulation of NCAM expression and polysialylation plays a key role on spatial memory.Eur J Neurosci,2006;23(6):1585-1595
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