兴奋
神经退行性变
细胞应激反应
信号转导
神经保护
生物
蛋白质稳态
热休克蛋白
细胞生物学
氧化应激
热冲击
硫氧还蛋白
神经科学
医学
生物化学
战斗或逃跑反应
疾病
基因
病理
作者
Vittorio Calabrese,Carolin Cornelius,Albena T. Dinkova‐Kostova,Edward J. Calabrese
出处
期刊:Biofactors
[Wiley]
日期:2009-03-01
卷期号:35 (2): 146-160
被引量:115
摘要
Modulation of endogenous cellular defense mechanisms via the stress response signaling represents an innovative approach to therapeutic intervention in diseases causing chronic damage, such as neurodegeneration and cancer. Protein thiols play a key role in redox sensing, and regulation of cellular redox state is crucial mediator of multiple metabolic, signaling, and transcriptional processes. Maintenance of optimal long-term health conditions is accomplished by a complex network of longevity assurance processes that are controlled by vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin, and the sirtuin protein systems. Dietary antioxidants, such as polyphenols and L-carnitine/acetyl-L-carnitine, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose-response, challenges long-standing beliefs about the nature of the dose-response in a low dose zone, having the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response, there is now strong interest in discovering and developing pharmacological agents capable of inducing these responses. In this review we discuss the most current and up-to-date understanding of the possible signaling mechanisms by which acetylcarnitine by activating vitagenes can differentially modulate signal transduction cascades inducing apoptosis/cell death in abnormal cancer cells but at the same time enhancing defensive enzymes to protect against carcinogenesis and neurodegeneration in normal cells. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.
科研通智能强力驱动
Strongly Powered by AbleSci AI