USDA-ARS, Human Nutrition Research Center on Aging at Tufts University, Boston MA 02111, USA.
J Nutr Biochem. 2013 May;24(5):912-9. doi: 10.1016/j.jnutbio.2012.06.009. Epub 2012 Aug 20.
An increase in the aggregation of misfolded/damaged polyubiquitinated proteins has been the hallmark of many age-related neurodegenerative diseases. The accumulation of these potentially toxic proteins in brain increases with age, in part due to increased oxidative and inflammatory stresses. Walnuts, rich in omega fatty acids, have been shown to improve memory, cognition and neuronal effects related to oxidative stress (OS) and inflammation (INF) in animals and human trials. The current study found that feeding 19-month-old rats with a 6% or 9% walnut diet significantly reduced the aggregation of polyubiquitinated proteins and activated autophagy, a neuronal housekeeping function, in the striatum and hippocampus. Walnut-fed animals exhibited up-regulation of autophagy through inhibiting phosphorylation of mTOR, up-regulating ATG7 and Beclin 1, and turnover of MAP1BLC3 proteins. The clearance of polyubiquitinated protein aggregates such as p62/SQSTM1 was more profound in hippocampus, a critical region in the brain involved in memory and cognitive performance, than striatum. The clearance of ubiquitinated aggregates was in tandem with significant reductions in OS/INF, as indicated by the levels of P38-MAP kinase and phosphorylations of nuclear factor kappa B and cyclic AMP response element binding protein. The results demonstrate the effectiveness of a walnut-supplemented diet in activating the autophagy function in brain beyond its traditionally known antioxidant and anti-inflammatory benefits.
蛋白质错误折叠/损伤导致的聚集体的增加，一直是许多与年龄相关的神经退行性疾病的主要特征。这些潜在毒性蛋白质在大脑中的积累随着年龄的增长而增加，部分原因是氧化和炎症应激的增加。研究表明，核桃富含欧米伽脂肪酸，可改善动物和人类试验中与氧化应激（OS）和炎症（INF）相关的记忆、认知和神经元效应。本研究发现，用 6%或 9%的核桃饮食喂养 19 个月大的大鼠，可显著减少纹状体和海马体中聚泛素化蛋白的聚集，并激活自噬，这是一种神经元维护功能。核桃喂养的动物通过抑制 mTOR 的磷酸化、上调 ATG7 和 Beclin 1 以及 MAP1BLC3 蛋白的周转来上调自噬。在海马体（大脑中与记忆和认知表现有关的关键区域）中，多泛素化蛋白聚集体（如 p62/SQSTM1）的清除比纹状体更为明显。泛素化聚集体的清除与 OS/INF 的显著减少平行，这表明 P38-MAP 激酶的水平以及核因子 kappa B 和环 AMP 反应元件结合蛋白的磷酸化。结果表明，核桃补充饮食在激活大脑自噬功能方面的有效性超出了其传统上已知的抗氧化和抗炎益处。
