Di Matteo Vincenzo, Esposito Ennio
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro (Chieti), Italy.
Curr Drug Targets CNS Neurol Disord. 2003 Apr;2(2):95-107. doi: 10.2174/1568007033482959.
Aging is a major risk factor for neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). An unbalanced overproduction of reactive oxygen species (ROS) may give rise to oxidative stress which can induce neuronal damage, ultimately leading to neuronal death by apoptosis or necrosis. A large body of evidence indicates that oxidative stress is involved in the pathogenesis of AD, PD, and ALS. Several studies have shown that nutritional antioxidants (especially vitamin E and polyphenols) can block neuronal death in vitro, and may have therapeutic properties in animal models of neurodegenerative diseases including AD, PD, and ALS. Moreover, clinical data suggest that nutritional antioxidants might exert some protective effect against AD, PD, and ALS. In this paper, the biochemical mechanisms by which nutritional antioxidants can reduce or block neuronal death occurring in neurodegenerative disorders are reviewed. Particular emphasis will be given to the role played by the nuclear transcription factor -kB (NF-kB) in apoptosis, and in the pathogenesis of neurodegenerative disorders, such as AD, PD, and ALS. The effects of ROS and antioxidants on NF-kB function and their relevance in the pathophysiology of neurodegenerative diseases will also be examined.
衰老 是包括阿尔茨海默病（AD）、帕金森病（PD）和肌萎缩侧索硬化症（ALS）在内的神经退行性疾病的主要风险因素。活性氧（ROS）的过度产生失衡可能导致氧化应激，进而诱导神经元损伤，最终通过凋亡或坏死导致神经元死亡。大量证据表明，氧化应激参与了AD、PD和ALS的发病机制。多项研究表明，营养性抗氧化剂（尤其是维生素E和多酚）在体外可阻止神经元死亡，并且在包括AD、PD和ALS在内的神经退行性疾病动物模型中可能具有治疗作用。此外，临床数据表明，营养性抗氧化剂可能对AD、PD和ALS发挥一定的保护作用。本文综述了营养性抗氧化剂可减少或阻止神经退行性疾病中神经元死亡的生化机制。将特别强调核转录因子 -κB（NF-κB）在凋亡以及AD、PD和ALS等神经退行性疾病发病机制中所起的作用。还将研究ROS和抗氧化剂对NF-κB功能的影响及其在神经退行性疾病病理生理学中的相关性。
