The Potential Therapeutic Effects of THC on Alzheimer's Disease
The Potential Therapeutic Effects of THC on Alzheimer's Disease
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DOI：
10.3233/jad-140093
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发表时间：
2014-01-01
影响因子：
4
通讯作者：
Cai, Jianfeng
中科院分区：
文献类型：
--
作者：
Cao, Chuanhai;Li, Yaqiong;Cai, Jianfeng
本研究的目的是研究Delta（9）-四氢大麻酚（THC）在减缓或停止阿尔茨海默病标志性特征方面的潜在治疗质量。将N2 a-变体淀粉样蛋白-β蛋白前体（A β PP）细胞与THC一起孵育，并在6小时、24小时和48小时时间标记处测定淀粉样蛋白-β（A β）水平。还测试了THC与咖啡因在N2 a/A β PPswe细胞中A β水平降低方面的协同作用。还测试了THC，以确定多种治疗是否有益。MTT法检测THC的毒性。进行硫磺素T测定和蛋白质印迹以测试THC的直接抗A β聚集显著性。最后，测试THC以确定其对糖原合成酶激酶-3 β（GSK-3 β）和相关信号传导通路的影响。从结果中，我们发现THC在极低浓度下以剂量依赖性方式有效降低N2 a/A β PPswe细胞中的A β水平。然而，咖啡因和THC结合在一起没有发现累加效应。我们确实发现THC直接与A β肽相互作用，从而抑制聚集。此外，THC在低浓度下以剂量依赖性方式有效降低总GSK-3 β水平和磷酸化GSK-3 β。在给药浓度下，未观察到毒性，CB 1受体未显著上调。此外，低剂量的THC可以增强线粒体功能，并且不抑制褪黑激素对线粒体功能的增强。这些数据强烈表明，THC可能是通过多种功能和途径治疗阿尔茨海默病的潜在治疗选择。
The purpose of this study was to investigate the potential therapeutic qualities of Delta(9)-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer's disease. N2a-variant amyloid-beta protein precursor (A beta PP) cells were incubated with THC and assayed for amyloid-beta (A beta) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the A beta level in N2a/A beta PPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-A beta aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3 beta (GSK-3 beta) and related signaling pathways. From the results, we have discovered THC to be effective at lowering A beta levels in N2a/A beta PPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with A beta peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3 beta levels and phosphorylated GSK-3 beta in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin's enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer's disease through multiple functions and pathways.