| 摘要: | 阿茲海默症為常見的失智症類型，主要病因為細胞內的 tau 過磷酸
化和 Aβ (Amyloid β) 累積過多，使得大腦神經元失去正常功能而凋亡。
文獻顯示，過多的 tau 過磷酸化和 Aβ 會使神經元所需的神經滋養因子
分泌下降，為導致神經細胞凋亡的原因之一。在體外神經細胞實驗中，
1,25(OH)2D3 可顯著提高 Glial cell line-derived neurotrophic factor (GDNF)的表現量。GDNF 可以透過活化細胞內 phosphatidylinositol 3-kinase /
protein kinase B (PI3K/Akt) 以降低 tau 過磷酸化和細胞凋亡。因此，本研究將於人類神經纖維瘤母細胞株 (Human neuroblastoma cell line,
SH-SY5Y) 加入 1,25(OH)2D3 與 Aβ，觀察 1,25(OH)2D3 對 Aβ 於細胞
造成之傷害，是否具有預防及改善作用。結果顯示，在 Aβ 傷害前給予
1,25(OH)2D3 介入，與未介入 1,25(OH)2D3 組相比，可提高 GDNF 表現、
活化 PI3K/Akt、降低 tau 過磷酸化且降低細胞凋亡。在 Aβ 傷害下給予
1,25(OH)2D3 與未介入 1,25(OH)2D3 組相比，可提高 GDNF 表現、活化
PI3K /Akt、降低 tau 過磷酸化且降低細胞凋亡。綜合上述結果顯示，
1,25(OH)2D3 可透過提高 GDNF 的表現以活化 PI3K/Akt 路徑，降低
tau 過磷酸化與細胞凋亡，具有預防及改善 Aβ 對細胞造成之傷害。
The causes of alzheimer’s disease are accumulation of Aβ and
intracellular tau protein hyperphosphorylation in brain, leading to neuron dysfunctions and cell apoptosis. The neurotrophic factors decreasing that result in cell apoptosis is caused by the accumulation of Aβ. According to the recent studies, 1,25(OH)2D3 increased the protein expression of GDNF that can support the neuron survive in primary neuron culture. In Enteric neuroblasts, GDNF active the PI3K / Akt pathway to phosphorylate Glycogen synthase kinase-3β (GSK-3β) at ser-9 position, decreasing cell apoptosis and tau protein hyperphosphorylation. The propose of this study was to investigate the neuroprotection of 1,25(OH)2D3 toward the cell treated with Aβ. We found that 1,25(OH)2D3 increased the the protein expression of GDNF,activing the PI3K /Akt pathway and decreased the cell apoptosis and tau protein hyperphosphorylation in SH-SY5Y human neuroblastoma cell which is treated with Aβ before or after 1,25(OH)2D3 treatment. 1,25(OH)2D3 can protect and ameliorate the damage caused by Aβ in SH-SY5Y human neuroblastoma cell. |
