Clinical development of curcumin in neurodegenerative disease.
Clinical development of curcumin in neurodegenerative disease.
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DOI：
10.1586/14737175.2015.1044981
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发表时间：
2015-06
影响因子：
4.3
通讯作者：
Frautschy SA
中科院分区：
文献类型：
--
作者：
Hu S;Maiti P;Ma Q;Zuo X;Jones MR;Cole GM;Frautschy SA
姜黄素是一种从姜黄根中提取的多酚类抗氧化剂，在伤口修复、癌症和炎症疾病中显示出显著的疗效，已经进行了广泛的临床前研究。本文综述了其用于神经退行性疾病，特别是阿尔茨海默病（AD）的基本原理。姜黄素是一种多效性分子，它不仅能直接结合并限制许多神经退行性疾病特有的淀粉样蛋白β-片构象的聚集，而且还能恢复炎症系统的稳态，促进热休克系统增强毒性聚集物的清除，清除自由基，螯合铁并诱导抗氧化反应元件。虽然姜黄素纠正了多种途径的失调，但它可能通过几个分子靶点发挥多种作用。姜黄素等天然化合物及其合成衍生物的药物开发具有强大的科学依据，但需要克服各种障碍，包括；试验成本高，对盈利能力的担忧以及对药物特异性、稳定性和生物利用度的误解。
Curcumin, a polyphenolic antioxidant derived from the turmeric root has undergone extensive preclinical development, showing remarkable efficacy in wound repair, cancer and inflammatory disorders. This review addresses the rationale for its use in neurodegenerative disease, particularly Alzheimer’s disease (AD). Curcumin is a pleiotropic molecule, which not only directly binds to and limits aggregation of the β-sheet conformations of amyloid characteristic of many neurodegenerative diseases but also restores homeostasis of the inflammatory system, boosts the heat shock system to enhance clearance of toxic aggregates, scavenges free radicals, chelates iron and induces anti-oxidant response elements. Although curcumin corrects dysregulation of multiple pathways, it may exert many effects via a few molecular targets. Pharmaceutical development of natural compounds like curcumin and synthetic derivatives have strong scientific rationale, but will require overcoming various hurdles including; high cost of trials, concern about profitability and misconceptions about drug specificity, stability and bioavailability.