Mancuso Cesare, Bates Timothy E, Butterfield D Allan, Calafato Stella, Cornelius Carolin, De Lorenzo Antonino, Dinkova Kostova Albena T, Calabrese Vittorio
Catholic University School of Medicine, Institute of Pharmacology, Largo F Vito, 00168 Roma, Italy.
Expert Opin Investig Drugs. 2007 Dec;16(12):1921-31. doi: 10.1517/13543784.16.12.1921.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by severe cognitive impairment that ultimately leads to death. Current drugs used in AD are acetylcholinesterase inhibitors and antagonists to the NMDA receptors. These drugs may only slightly improve cognitive functions but have only very limited impact on the clinical course of the disease. In the past several years, based on in vitro and in vivo studies in laboratory animals, natural antioxidants, such as resveratrol, curcumin and acetyl-L-carnitine have been proposed as alternative therapeutic agents for AD. An increasing number of studies demonstrated the efficacy of primary antioxidants, such as polyphenols, or secondary antioxidants, such as acetylcarnitine, to reduce or to block neuronal death occurring in the pathophysiology of this disorder. These studies revealed that other mechanisms than the antioxidant activities could be involved in the neuroprotective effect of these compounds. This paper discusses the evidence for the role of acetylcarnitine in modulating redox-dependent mechanisms leading to the upregulation of vitagenes. Furthermore, future development of novel antioxidant drugs targeted to the mitochondria should result in effectively slowing disease progression. The association with new drug delivery systems may be desirable and useful for the therapeutic use of antioxidants in human neurodegenerative diseases.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是严重的认知障碍，最终导致死亡。目前用于治疗AD的药物是乙酰胆碱酯酶抑制剂和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂。这些药物可能只能轻微改善认知功能，但对疾病的临床进程影响非常有限。在过去几年中，基于对实验动物的体外和体内研究，白藜芦醇、姜黄素和乙酰-L-肉碱等天然抗氧化剂已被提议作为AD的替代治疗药物。越来越多的研究表明，初级抗氧化剂（如多酚）或次级抗氧化剂（如乙酰肉碱）在减少或阻止该疾病病理生理学中发生的神经元死亡方面具有疗效。这些研究表明，这些化合物的神经保护作用可能涉及抗氧化活性以外的其他机制。本文讨论了乙酰肉碱在调节导致维甲酸上调的氧化还原依赖性机制中的作用证据。此外，针对线粒体的新型抗氧化药物的未来发展应能有效减缓疾病进展。与新的药物递送系统相结合可能对人类神经退行性疾病中抗氧化剂的治疗应用是可取和有用的。
