Danish Research Institute of Translational Neuroscience, Nordic EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
Molecular Neurobiology Group, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal.
Int J Mol Sci. 2019 Mar 14;20(6):1287. doi: 10.3390/ijms20061287.
Transthyretin (TTR) amyloidoses (ATTR amyloidosis) are diseases associated with transthyretin (TTR) misfolding, aggregation and extracellular deposition in tissues as amyloid. Clinical manifestations of the disease are variable and include mainly polyneuropathy and/or cardiomyopathy. The reasons why TTR forms aggregates and amyloid are related with amino acid substitutions in the protein due to mutations, or with environmental alterations associated with aging, that make the protein more unstable and prone to aggregation. According to this model, several therapeutic approaches have been proposed for the diseases that range from stabilization of TTR, using chemical chaperones, to clearance of the aggregated protein deposited in tissues in the form of oligomers or small aggregates, by the action of disruptors or by activation of the immune system. Interestingly, different studies revealed that curcumin presents anti-amyloid properties, targeting multiple steps in the ATTR amyloidogenic cascade. The effects of curcumin on ATTR amyloidosis will be reviewed and discussed in the current work in order to contribute to knowledge of the molecular mechanisms involved in TTR amyloidosis and propose more efficient drugs for therapy.
转甲状腺素蛋白(TTR)淀粉样变(ATTR 淀粉样变)是与转甲状腺素蛋白(TTR)错误折叠、聚集和细胞外沉积为淀粉样物质相关的疾病。该疾病的临床表现多种多样,主要包括多发性神经病和/或心肌病。TTR 形成聚集物和淀粉样物质的原因与由于突变导致的蛋白质中的氨基酸取代有关,或与与衰老相关的环境改变有关,这些改变使蛋白质更不稳定,更容易聚集。根据该模型,已经提出了几种针对这些疾病的治疗方法,范围从 TTR 的稳定化,使用化学伴侣,到以寡聚物或小聚集体的形式清除沉积在组织中的聚集蛋白,通过破坏剂或激活免疫系统的作用。有趣的是,不同的研究表明姜黄素具有抗淀粉样特性,针对 ATTR 淀粉样变级联反应的多个步骤。本文将综述和讨论姜黄素对 ATTR 淀粉样变的作用,以促进对 TTR 淀粉样变相关分子机制的认识,并为治疗提出更有效的药物。