Gupta Veer Bala, Rao K S J
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570020, India.
Neurosci Lett. 2007 Dec 18;429(2-3):75-80. doi: 10.1016/j.neulet.2007.09.042. Epub 2007 Sep 29.
Alzheimer's disease involves Abeta accumulation, oxidative damage and inflammation and there is currently no clinically accepted treatment to stop its progression. Its risk is known to reduce with increased consumption of antioxidant and anti-inflammatory agents. Fibrillar aggregates of Abeta are major constituents of the senile plaques found in the brains of AD patients and have been related to AD neurotoxicity. It is reported that SAC (S-allyl-l-cysteine), a water-soluble organosulfur component present in garlic is known to prevent cognitive decline by protecting neurons from Abeta induced neuronal apoptosis. Hence, we investigated the effects of SAC on Abeta aggregation by employing Thioflavin-T, transmission electron microscopy, SDS-PAGE, size exclusion-HPLC. Under aggregating conditions in vitro, SAC dose-dependently inhibited Abeta fibrillation and also destabilized preformed Abeta fibrils. Further, Circular dichroism and fluorescence quenching studies supported the binding ability of SAC to Abeta and inducing a partially folded conformation in Abeta. The 3D structure of Abeta-SAC complex was also predicted employing automated docking studies.
阿尔茨海默病涉及β-淀粉样蛋白（Aβ）聚集、氧化损伤和炎症，目前尚无临床上被认可的阻止其进展的治疗方法。已知随着抗氧化剂和抗炎剂摄入量的增加，其风险会降低。Aβ的纤维状聚集体是阿尔茨海默病患者大脑中发现的老年斑的主要成分，并且与阿尔茨海默病神经毒性有关。据报道，大蒜中存在的一种水溶性有机硫成分S-烯丙基-L-半胱氨酸（SAC）可通过保护神经元免受Aβ诱导的神经元凋亡来预防认知能力下降。因此，我们通过使用硫黄素-T、透射电子显微镜、十二烷基硫酸钠-聚丙烯酰胺凝胶电泳、尺寸排阻高效液相色谱法研究了SAC对Aβ聚集的影响。在体外聚集条件下，SAC剂量依赖性地抑制Aβ纤维化，并且还使预先形成的Aβ纤维不稳定。此外，圆二色性和荧光猝灭研究支持SAC与Aβ的结合能力，并在Aβ中诱导部分折叠构象。还采用自动对接研究预测了Aβ-SAC复合物 的三维结构。
