Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Brain Res. 2019 Feb 1;1704:78-84. doi: 10.1016/j.brainres.2018.10.001. Epub 2018 Oct 1.
Alzheimer's disease (AD), affecting 5.3 million people in the U.S., impairs portions of the brain controlling memories. In humans, mutations in the amyloid precursor protein (APP) gene has been implicated in increased plaque formation, which can block the communication between nerve cells, decrease dendritic formation and increase cell death, and promote neuroinflammation. As coconut oil has been suggested to alleviate the symptoms in AD patients, we examined the impact of coconut oil on APP expression and secretion of amyloid peptides in N2a cells expressing the human APP gene (N2a/APP695). We found that coconut oil treatment decreased APP expression in N2a cells and reduced the secretion of amyloid peptides Aβ and Aβ. Moreover, coconut oil treatment promoted differentiation of N2a cells. Our data suggest that ADP-Ribosylation Factor 1 (ARF1) may contribute to the effects of coconut oil on APP expression and secretion of Aβ. A high ARF1 expression was also detected in the primary neuronal cells from the mice overexpressing the Swedish mutant APP. Immunostaining results revealed that APP is co-localized with ARF1 in the Golgi apparatus and this interaction is impaired after coconut oil treatment. Furthermore, knockdown of ARF-1 using siRNA decreased secretion of amyloid peptides, confirming the impact of ARF1 on the secretion of amyloid peptides. CONCLUSION: These results suggest that coconut oil decreases intracellular ARF1 expression, thereby resulting in an inhibition of APP and amyloid β secretion. This study reveals a novel mechanism for intracellular APP processing in neuronal cells.
阿尔茨海默病（AD）影响了美国 530 万人，损害了大脑中控制记忆的部分。在人类中，淀粉样前体蛋白（APP）基因突变与斑块形成增加有关，这会阻断神经细胞之间的通讯，减少树突形成，增加细胞死亡，并促进神经炎症。由于椰子油被认为可以缓解 AD 患者的症状，我们研究了椰子油对表达人 APP 基因的 N2a 细胞（N2a/APP695）中 APP 表达和淀粉样肽分泌的影响。我们发现椰子油处理可降低 N2a 细胞中的 APP 表达，并减少淀粉样肽 Aβ和 Aβ的分泌。此外，椰子油处理可促进 N2a 细胞的分化。我们的数据表明，ADP-核糖基化因子 1（ARF1）可能有助于椰子油对 APP 表达和 Aβ分泌的影响。在过表达瑞典突变 APP 的小鼠的原代神经元细胞中也检测到高 ARF1 表达。免疫染色结果显示，APP 与高尔基体中的 ARF1 共定位，并且这种相互作用在椰子油处理后受损。此外，使用 siRNA 敲低 ARF-1 可减少淀粉样肽的分泌，证实了 ARF1 对淀粉样肽分泌的影响。结论：这些结果表明，椰子油降低了细胞内 ARF1 的表达，从而抑制了 APP 和淀粉样 β 的分泌。这项研究揭示了神经元细胞中细胞内 APP 加工的新机制。
