姜黄素衍生物对无金属和金属诱导的β-淀粉样蛋白聚合物的抑制活性

Title:Inhibitory Activity of Curcumin Derivatives Towards Metal-Free and Metal-Induced Amyloid-β Aggregation

Volume: 12 Issue: 5

Author(s): Akiko Kochi, Hyuck Jin Lee, Sashiprabha M. Vithanarachchi, Vediappen Padmini, Matthew J. Allen and Mi Hee Lim

Affiliation:

关键词: 阿尔茨海默氏病；β-淀粉样蛋白；金属-Aβ联合物种；β-淀粉样蛋白聚合调控；水溶性姜黄素衍生物；化学试剂

摘要: When Alzheimer’s disease (AD) progresses, several pathological features arise including accumulation of misfolded protein aggregates [e.g., amyloid-β (Aβ) plaques], metal ion dyshomeostasis, and oxidative stress. These characteristics are recently suggested to be interconnected through a potential factor, metal-associated Aβ (metal−Aβ) species. The role of metal–Aβ species in AD pathogenesis remains unclear, however. To elucidate the contribution of metal–Aβ species to AD pathology, as well as to develop small molecules as chemical tools and/or theranostic (therapeutic and diagnostic) agents for this disease, curcumin (Cur), a natural product from turmeric, and its derivatives have been studied towards both metal-free and metal-induced Aβ aggregation. Although Cur has indicated anti-amyloidogenic activities and antioxidant properties, its biological use has been hindered due to low solubility and stability in physiologically relevant conditions. Herein, we report the reactivity of Cur and its derivatives (Gd-Cur, a potential multimodal Aβ imaging agent; Cur-S, a water soluble derivative of Cur that has substitution at the phenolic hydroxyls) with metal-free Aβ and metal−Aβ species. Our results and observations indicate that Gd-Cur could modulate Cu(II)-triggered Aβ aggregation more noticeably over metal-free or Zn(II)-induced analogues; however, Cur-S was not observed to noticeably modulate Aβ aggregation with and without metal ions. Overall, our studies present information that could aid in optimizing the molecular scaffold of Cur for the development of chemical tools or theranostics for metal−Aβ species.

Cite this article as:

Akiko Kochi, Hyuck Jin Lee, Sashiprabha M. Vithanarachchi, Vediappen Padmini, Matthew J. Allen and Mi Hee Lim , Inhibitory Activity of Curcumin Derivatives Towards Metal-Free and Metal-Induced Amyloid-β Aggregation, Current Alzheimer Research 2015; 12 (5) . https://dx.doi.org/10.2174/1567205012666150504150125