近期有研究指出氧化型態之半乳糖凝集蛋白-1（GAL-1）及活化肝X受體（LXRs）在中樞神經系統及神經細胞中具減緩發炎反應之效果。此外，也有學者指出GAL-1 及LXRs與幹細胞之增生和分化作用息息相關。在本篇研究中我們利用過度表現之氧化型態GAL-1及LXR活化劑（TO901317）進一步探討對於N2A cells之神經保護機制以及對於人類神經幹細胞（hNSCs）之影響。在我們的研究結果顯示分別經由利用給予GAL1和LXR活化劑處理作用之下，其在N2A cells中具顯著促進神經細胞之軸突生長以及抑制腫瘤壞死因子α(TNF-α)所誘導之毒性的效果。而GAL1和LXR活化劑主要為可有效地減少腫瘤壞死因子α所誘導之核因子-B（NF-B）的表現和及顯著地抑制NF-B易位進入細胞核內表現，在其作用機制中我們證明GAL-1和LXR活化劑可經由透過阻斷NF-κB活化減少細胞發炎因子如環氧化酶（COX-2）、誘導型一氧化氮合成酶（iNOS）之表現進一步降低發炎反應。此外，我們也發現GAL-1和LXR活化劑在人類神經幹細胞中之作用其可增加MAP2(神經元細胞標誌）之表現。經由我們的研究結果証明GAL-1和LXR活化劑在N2A cells之神經保護作用中確實扮演著重要的角色並且具有誘導人類神經幹細胞分化為神經元細胞之潛力。
Recent investigations suggest that oxidized Galectin-1 (GAL-1) and activation of liver X receptors ( LXRs ) attenuate the inflammatory response of neural cells. The current studies further characterize the mechanism of neural protection of GAL- 1and LXR agonist in N2A cells and human neural stem cells (hNSCs). The results showed that GAL1 and LXR agonist (TO901317) significantly promoted neurite outgrowth and suppressed tumor necrosis factor-α(TNF-α) induced toxicity. The current studies also showed that GAL1 and LXR agonist treatment could inhibit TNF-α induced nuclear factor-κB(NF-κB) expression and translocation into nucleus. In addition, we have been demonstrated that GAL-1 and LXR agonist could reduce proinflammatory cytokines such as cyclo-oxygenase-2 (COX-2) and inductible Nitric Oxide Synthase (iNOS) expression via blocking NF-κB activation. These results suggest that the protective role of GAL-1 and LXR agonist in N2A cells was mediated through the suppression of NF-κB activation. Moreover, GAL-1 and LXR agonist also induced the expression of microtubule associated protein 2 (MAP2) in hNSCs. These results suggest that GAL-1 and LXR agonist plays important role neuroprotection in N2A cells and induces in hNSCs differentiation into neuronal cells.
