The presence of acrylamide (ACR) in food results in evident cognitive decline, accumulation of misfolded proteins, neurotoxicity, neuroinflammation, and neuronal apoptosis leading to progressive neurodegeneration. Here, we used 4 dpf zebrafish larvae exposed to ACR (1mM/3days) as our model, and neuronal proteins were analyzed. Next, we tested the effect of garcinol (GAR), a natural histone-acetylation inhibitor, whose neuroprotection mechanism of action remains to be fully elucidated. Our result revealed that ACR exposure significantly impaired cognitive behavior, downregulated oxidative repair machinery, and enhanced microglia-induced neuronal apoptosis. Moreover, ACR mediated cathepsin-B (CAT-B) translocation acted as the intracellular secretase for the processing of amyloid precursor protein (APP) and served as an additional risk factor for tau hyper-phosphorylation. Here, GAR suppresses ACR mediated CATB translocation as similar with standard inhibitor CA-074. And, this pharmacological repression helped in inhibiting amyloidogenic APP processing and downstream tau hyper-phosphorylation. GAR neuroprotection was accompanied by CREB, ATF1, and BDNF activation promoting neuronal survival. At the same time, GAR subdued cdk5 and GSK3β, the link between APP processing and tau hyper-phosphorylation. Taken together, our findings indicate that GAR rescued from ACR mediated behavioral defects, oxidative injury, neuroinflammation, undesirable APP processing, tau hyper-phosphorylation which in turn found to be CATB dependent.

食物中丙烯酰胺（ACR）的存在会导致明显的认知能力下降，蛋白质折叠错误，神经毒性，神经炎症和神经元凋亡，从而导致进行性神经变性。在这里，我们使用4 dpf斑马鱼幼虫暴露于ACR（1mM / 3天）作为模型，并分析了神经元蛋白。接下来，我们测试了藤黄素（GAR）的作用，这是一种天然的组蛋白乙酰化抑制剂，其神经保护作用机理尚待充分阐明。我们的结果表明，暴露于ACR会严重损害认知行为，下调氧化修复机制并增强小胶质细胞诱导的神经元凋亡。此外，ACR介导的组织蛋白酶B（CAT-B）易位充当淀粉样前体蛋白（APP）加工的细胞内分泌酶，并且是tau过度磷酸化的另一个危险因素。在这里，与标准抑制剂CA-074相似，GAR抑制ACR介导的CATB转运。并且，这种药理学抑制作用有助于抑制淀粉样蛋白原APP加工和下游tau过度磷酸化。GAR神经保护作用伴有CREB，ATF1和BDNF激活，从而促进神经元存活。同时，GAR抑制了cdk5和GSK3β（APP处理与tau超磷酸化之间的联系）。综上所述，我们的发现表明GAR可从ACR介导的行为缺陷，氧化损伤，神经炎症，不良的APP处理，