Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, 105-8512, Japan.
Department of Pharmaceutical and Health Sciences, Josai University, Saitama, Japan.
Mol Nutr Food Res. 2018 Nov;62(21):e1800238. doi: 10.1002/mnfr.201800238. Epub 2018 Sep 9.
Epidemiological studies have shown that coffee consumption may be associated with a lower risk of developing several neurological disorders, including Alzheimer's disease (AD). Caffeine is a prominent candidate component underlying the preventive effects of coffee; however, the contribution of other constituents is unclear. To clarify this issue, the effect of roasting coffee beans on β-secretase (BACE1) expression in human neuroblastoma SH-SY5Y cells is investigated.
Coffee (2%) reduces Aβ accumulation in culture medium to 80% of control levels after 24 h. Accordingly, BACE1 expression is decreased to 70% of control levels at 12 h. Experiments using cycloheximide and MG132, a proteasome inhibitor, reveal that coffee enhanced BACE1 degradation through activation of proteasomal activity. Furthermore, coffee activates cAMP-dependent protein kinase, and consequently, phosphorylation of a serine residue of proteasome 26S subunit, non-ATPase 11 (PSMD11). Pyrocatechol, a strong antioxidant known as catechol or 1,2-dihydroxybenzene, produced from chlorogenic acid during roasting, also reduces BACE1 expression by activation of proteasomal activity. Furthermore, pyrocatechol reduces Aβ production in SH-SY5Y cells.
The data suggest that the roasting process may be crucial for the protective effects of coffee consumption in AD.
流行病学研究表明，咖啡的摄入可能与多种神经退行性疾病（包括阿尔茨海默病）的发病风险降低有关。咖啡因是咖啡发挥预防作用的主要候选成分；然而，其他成分的贡献尚不清楚。为了阐明这个问题，本研究调查了烘焙咖啡豆对人神经母细胞瘤 SH-SY5Y 细胞中β-分泌酶（BACE1）表达的影响。
咖啡（2%）可使培养物中 Aβ的积累在 24 小时后减少至对照水平的 80%。相应地，BACE1 的表达在 12 小时后降低至对照水平的 70%。使用环己酰亚胺和蛋白酶体抑制剂 MG132 的实验表明，咖啡通过激活蛋白酶体活性增强 BACE1 的降解。此外，咖啡激活 cAMP 依赖性蛋白激酶，从而磷酸化蛋白酶体 26S 亚基非 ATP 酶 11（PSMD11）的丝氨酸残基。儿茶酚，一种在烘焙过程中由绿原酸产生的强抗氧化剂，也称为邻苯二酚或 1,2-二羟基苯，通过激活蛋白酶体活性来降低 BACE1 的表达。此外，儿茶酚可减少 SH-SY5Y 细胞中的 Aβ 产生。
数据表明，烘焙过程可能对咖啡摄入在 AD 中的保护作用至关重要。
