UNASSIGNED: Cinnamein, a nontoxic compound, is naturally available in Balsam of Peru and Tolu Balsam. We examined whether cinnamein treatment could decrease plaques and improve cognitive functions in 5XFAD mouse model of AD.
UNASSIGNED: We employed in silico analysis, time-resolved fluorescence energy transfer assay, thermal shift assay, primary neuron isolation, western blot, immunostaining, immunohistochemistry, Barnes maze, T maze, and open field behavior.
UNASSIGNED: Oral administration of cinnamein led to significant reduction in amyloid-β plaque deposits in the brain and protection of spatial learning and memory in 5XFAD mice. Peroxisome proliferator-activated receptor alpha (PPARα), a nuclear hormone receptor, is involved in plaque lowering and increase in hippocampal plasticity. While investigating underlying mechanisms, we found that cinnamein served as a ligand of PPARα. Accordingly, oral cinnamein upregulated the level of PPARα, but not PPARβ, in the hippocampus, and remained unable to decrease plaques from the hippocampus and improve memory and learning in 5XFAD mice lacking PPARα. While A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is one of the drivers of nonamyloidogenic pathway, transcription factor EB (TFEB) is considered as the master regulator of autophagy. Cinnamein treatment was found to upregulate both ADAM10 and TFEB in the brain of 5XFAD mice via PPARα.
UNASSIGNED: Our results suggest that this balsam component may have therapeutic importance in AD.
■肉桂,一种无毒的化合物,在秘鲁香脂和Tolu香脂中天然可用。我们研究了肉桂素治疗是否可以减少AD的5XFAD小鼠模型中的斑块并改善认知功能。
■我们采用了硅分析,时间分辨荧光能量转移测定,热移位测定,初级神经元隔离,westernblot,免疫染色,免疫组织化学,巴恩斯迷宫,T迷宫,和开放领域的行为。
■口服肉桂素导致5XFAD小鼠脑中淀粉样蛋白-β斑块沉积的显著减少和空间学习和记忆的保护。过氧化物酶体增殖物激活受体α(PPARα),核激素受体,与斑块降低和海马可塑性增加有关。在调查潜在机制时,我们发现肉桂素是PPARα的配体。因此,口服肉桂素上调PPARα水平,但不是PPARβ,在海马中,并且仍然无法减少缺乏PPARα的5XFAD小鼠的海马斑块并改善记忆和学习。虽然含有解整合素和金属蛋白酶结构域的蛋白10(ADAM10)是非淀粉样蛋白形成途径的驱动因素之一,转录因子EB(TFEB)被认为是自噬的主要调节因子。发现肉桂素处理通过PPARα上调5XFAD小鼠脑中的ADAM10和TFEB。
■我们的结果表明,这种香脂成分可能在AD中具有治疗重要性。