Calabrese Vittorio, Cornelius Carolin, Mancuso Cesare, Barone Eugenio, Calafato Stella, Bates Timothy, Rizzarelli Enrico, Kostova Albena T Dinkova
Department of Chemistry, Biochemistry and Mol. Biology Section, Faculty of Medicine, University of Catania, Catania, Italy.
Front Biosci (Landmark Ed). 2009 Jan 1;14(1):376-97. doi: 10.2741/3250.
The ability of a cell to counteract stressful conditions, known as cellular stress response, requires the activation of pro-survival pathways and the production of molecules with anti-oxidant, anti-apoptotic or pro-apoptotic activities. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include heat shock proteins (Hsps) heme oxygenase-1 and Hsp70, as well as the thioredoxin/thioredoxin reductase system. Heat shock response contributes to establish a cytoprotective state in a wide variety of human diseases, including inflammation, cancer, aging and neurodegenerative disorders. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Dietary antioxidants, such as curcumin, L-carnitine/acetyl-L-carnitine and carnosine have recently been demonstrated in vitro to be neuroprotective through the activation of hormetic pathways, including vitagenes. In the present review we discuss the importance of vitagenes in the cellular stress response and analyse, from a pharmacological point of view, the potential use of dietary antioxidants in the treatment of neurodegenerative disorders in humans.
细胞抵抗应激条件的能力,即细胞应激反应,需要激活促生存途径并产生具有抗氧化、抗凋亡或促凋亡活性的分子。在赋予细胞抵抗氧化应激保护作用的细胞途径中,维他基因发挥着关键作用,其中包括热休克蛋白(Hsps)、血红素加氧酶-1和Hsp70,以及硫氧还蛋白/硫氧还蛋白还原酶系统。热休克反应有助于在包括炎症、癌症、衰老和神经退行性疾病在内的多种人类疾病中建立细胞保护状态。鉴于热休克反应具有广泛的细胞保护特性,目前人们对发现和开发能够诱导应激反应的药物制剂有着浓厚兴趣。膳食抗氧化剂,如姜黄素、L-肉碱/乙酰-L-肉碱和肌肽,最近在体外被证明可通过激活包括维他基因在内的应激反应途径而具有神经保护作用。在本综述中,我们讨论了维他基因在细胞应激反应中的重要性,并从药理学角度分析了膳食抗氧化剂在治疗人类神经退行性疾病中的潜在用途。