Nieto-Sampedro M, Muneton-Gomez V C
Hospital Nacional de Paraplejicos, 45071 Toledo, Espana.
CSIC. Instituto de Neurobiologia Ramon y Cajal, 28002 Madrid, Espana.
Rev Neurol. 2017 Jun 16;64(12):549-567.
Glial cells in the central nervous system of adult mammals outnumber neurons 10-fold. Their number remains stationary throughout adulthood, controlled by the concomitant presence of mitogens and mitogen inhibitors. The most abundant inhibitor, neurostatin, is ganglioside GD1b O-acetylated on hydroxyl 9 of its outermost sialic acid. Neurostatin inhibited the proliferation of primary microglia and astroblasts in culture (cytostatic) as well as both rodent and human glioma cells (cytotoxic) at nanomolar concentrations. At those concentrations neurostatin had no effect on non-glial lineage cells or differentiated glia. Neurostatin shows direct antimitotic activity on tumoral cells, interfering with multiple signals regulating cell cycle progression. But it also promotes indirectly total destruction of experimental rat brain glioma, presumably by making it visible to the host immune system and activating CD4+ and CD8+ lymphocytes. Neurostatin could be a new anti-inflammatory agent, with multiple convergent direct and indirect actions on glioma growth, a pathology without satisfactory clinical treatment. Neurostatin is produced by neurons but its expression is up-regulated by neuron-astrocyte contact. The action of neurostatin could be mediated by a number of receptor proteins, including integrins, Toll-like receptors and siglecs.
成年哺乳动物中枢神经系统中的神经胶质细胞数量比神经元多10倍。在整个成年期，它们的数量保持稳定，这是由有丝分裂原和有丝分裂原抑制剂的共同存在所控制的。最丰富的抑制剂神经抑素是其最外层唾液酸的9位羟基被O - 乙酰化的神经节苷脂GD1b。神经抑素在纳摩尔浓度下可抑制培养中的原代小胶质细胞和成纤维细胞的增殖（细胞抑制作用）以及啮齿动物和人类胶质瘤细胞的增殖（细胞毒性作用）。在这些浓度下，神经抑素对非神经胶质谱系细胞或分化的神经胶质细胞没有影响。神经抑素对肿瘤细胞具有直接的抗有丝分裂活性，干扰调节细胞周期进程的多种信号。但它也间接促进实验性大鼠脑胶质瘤的完全破坏，大概是通过使其对宿主免疫系统可见并激活CD4 +和CD8 +淋巴细胞来实现的。神经抑素可能是一种新的抗炎剂，对胶质瘤生长具有多种直接和间接的协同作用，而胶质瘤是一种尚无满意临床治疗方法的疾病。神经抑素由神经元产生，但其表达通过神经元与星形胶质细胞的接触而上调。神经抑素的作用可能由多种受体蛋白介导，包括整合素、Toll样受体和唾液酸结合免疫球蛋白样凝集素。
