Srinivasan Venkatramanujan
Department of Physiology, PSG Institute of Medical Sciences and Research, Coimbatore 641 004, India.
Indian J Exp Biol. 2002 Jun;40(6):668-79.
Oxidative Stress is implicated as one of the primary factors that contribute to the development of neurodegenerative diseases like Alzheimer's Disease, Parkinsonism and neurological conditions like epileptic seizures, stroke, brain damage, neurotrauma etc. The increased formation and release of oxygen free radicals coupled with the rather low antioxidative potential of the central nervous system are the major reasons that account for the enhanced oxidative stress seen in neuronal cells. In addition to this, brain is also enriched with polyunsaturated fatty acids that render neuronal cells easily vulnerable to oxidative attack. The fact that there is increased incidence of neurodegenerative disorders in aged individuals, has prompted many investigators to search for a common factor whose progressive decline with increase in age could account for increased oxidative stress resulting in senescence and age associated degenerative diseases. Since melatonin, the hormone secreted from the pineal gland has a remarkable anti-oxidant property and whose rate of production declines with increase in age, has prompted many to suggest that this hormone plays a crucial role in the genesis of neurodegenerative diseases. Melatonin cannot only scavenges oxygen free radicals like super oxide radical (O2-), hydroxyl radical (OH), peroxyl radical (LOO) and peroxynitrite anion (ONOO-), but can also enhance the antioxidative potential of the cell by stimulating the synthesis of antioxidative enzymes like super oxide dismutase (SOD), glutathione peroxidase (GPX), and also the enzymes that are involved in the synthesis of glutathione. In many instances, melatonin increases the expression of m RNA's of the antioxidative enzymes. Melatonin administration has been shown to be effective in counteracting the neurodegenerative conditions both in experimental models of neurodegenerative diseases and in patients suffering from such diseases. A disturbance of melatonin rhythm and secretion also has been noted in patients suffering from certain neurodegenerative diseases. From all these, it is evident that melatonin has a neuroprotective role.
氧化应激被认为是导致神经退行性疾病(如阿尔茨海默病、帕金森病)以及癫痫发作、中风、脑损伤、神经创伤等神经系统疾病发生的主要因素之一。氧自由基生成和释放增加,再加上中枢神经系统抗氧化能力较低,是神经元细胞中氧化应激增强的主要原因。除此之外,大脑富含多不饱和脂肪酸,这使得神经元细胞很容易受到氧化攻击。老年个体神经退行性疾病发病率增加这一事实,促使许多研究人员寻找一个共同因素,其随着年龄增长而逐渐下降可能导致氧化应激增加,进而引发衰老和与年龄相关的退行性疾病。由于松果体分泌的褪黑素具有显著的抗氧化特性,且其分泌率随年龄增长而下降,这促使许多人认为这种激素在神经退行性疾病的发生中起关键作用。褪黑素不仅可以清除超氧阴离子自由基(O2-)、羟基自由基(OH)、过氧自由基(LOO)和过氧亚硝酸根阴离子(ONOO-)等氧自由基,还可以通过刺激超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPX)等抗氧化酶的合成,以及参与谷胱甘肽合成的酶,来增强细胞的抗氧化能力。在许多情况下褪黑素会增加抗氧化酶mRNA的表达。在神经退行性疾病的实验模型和患有此类疾病的患者中,褪黑素给药已被证明能有效对抗神经退行性疾病。在患有某些神经退行性疾病的患者中也发现了褪黑素节律和分泌的紊乱。从所有这些情况来看,很明显褪黑素具有神经保护作用。