Cellular and Biomolecular Laboratory, Department of Chemical Engineering and Material Science, Michigan State University, East Lansing, MI 48824, USA.
Neurosci Lett. 2013 Oct 25;554:121-5. doi: 10.1016/j.neulet.2013.09.008. Epub 2013 Sep 11.
Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular deposits of amyloid beta (Aβ) protein and intracellular neurofibrillary tangles of hyperphosphorylated tau protein. Various studies suggest that the tau tangle pathology, which lies downstream to Aβ pathology, is essential to produce AD-associated clinical phenotype and thus treatments targeting tau pathology may prevent or delay disease progression effectively. In this context, our present study examined three polyphenol compounds (curcumin, EGCG and resveratrol) for their possible activity against two endogenous proteins (BAG2 and LAMP1) that are shown to play a vital role in clearing tau tangles from neurons. Human epidemiological and animal data suggest potential positive effects of these polyphenols against AD. Here, primary rat cortical neurons treated with these polyphenols significantly up-regulated BAG2 levels at different concentrations, while only EGCG upregulated LAMP1 levels, although at higher concentrations. Importantly, curcumin doubled BAG2 levels at low micromolar concentrations that are clinically relevant. In addition, curcumin also downregulated levels of phosphorylated tau, which may be potentially attributed to the curcumin-induced upregulation in BAG2 levels in the neurons. The present results demonstrate novel activity of polyphenol curcumin in up-regulating an anti-tau cochaperone BAG2 and thus, suggest probable benefit of curcumin against AD-associated tauopathy.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是细胞外淀粉样β（Aβ）蛋白沉积和细胞内过度磷酸化的tau 蛋白神经原纤维缠结。各种研究表明，位于 Aβ 病理学下游的 tau 缠结病理学对于产生与 AD 相关的临床表型至关重要，因此针对 tau 病理学的治疗方法可能有效预防或延迟疾病进展。在这种情况下，我们目前的研究检查了三种多酚化合物（姜黄素、EGCG 和白藜芦醇）对两种内源性蛋白质（BAG2 和 LAMP1）的可能活性，这些蛋白质被证明在清除神经元中的 tau 缠结中发挥着至关重要的作用。人类流行病学和动物数据表明这些多酚对 AD 具有潜在的积极作用。在这里，用这些多酚处理的原代大鼠皮质神经元在不同浓度下显著上调了 BAG2 水平，而只有 EGCG 上调了 LAMP1 水平，尽管在更高的浓度下。重要的是，姜黄素在低微摩尔浓度下将 BAG2 水平提高了一倍，这在临床上是相关的。此外，姜黄素还下调了磷酸化 tau 的水平，这可能归因于神经元中 BAG2 水平的姜黄素诱导上调。本研究结果表明多酚姜黄素在上调抗 tau 共伴侣 BAG2 方面具有新的活性，因此表明姜黄素对 AD 相关 tau 病可能有益。
