Maruyama Wakako, Shaomoto-Nagai Masayo, Kato Yoji, Hisaka Shinsuke, Osawa Toshihiko, Naoi Makoto
Department of Cognitive Brain Science, National Institute for Geriatrics and Gerontology, 35 Morioka, Obu, Aichi, 474-8511, Japan,
Subcell Biochem. 2014;77:127-36. doi: 10.1007/978-94-007-7920-4_11.
Nervous system controls all the organs in the living like a symphony. In this chapter, the mechanism of neuronal death in aged is discussed in relation to oxidative stress. Polyunsaturated fatty acid (PUFA) is known to be rich in the membranous component of the neurons and plays an important role in maintaining the neuronal functions. Recent reports revealed that oxidation of omega-3 and omega-6 PUFAs, such as docosahexaenoic acid (DHA) and arachidonic acid (ARA), are potent antioxidant but simultaneously, their oxidation products are potentially toxic. In this chapter, the existence of early oxidation products of PUFA is examined in the samples from neurodegenerative disorders and the cellular model. Accumulation of proteins with abnormal conformation is suggested to induce neuronal death by disturbance of proteolysis and mitochondrial function. The role of lipid peroxide and lipid-derived aldehyde adduct proteins is discussed in relation to brain ageing and age-related neurodegeneration.
神经系统如同交响乐指挥一般控制着生物体内的所有器官。在本章中,将探讨衰老过程中神经元死亡与氧化应激相关的机制。已知多不饱和脂肪酸(PUFA)在神经元的膜成分中含量丰富,并且在维持神经元功能方面发挥着重要作用。最近的报告显示,ω-3和ω-6多不饱和脂肪酸(如二十二碳六烯酸(DHA)和花生四烯酸(ARA))的氧化产物既是强大的抗氧化剂,但同时它们本身也可能具有毒性。在本章中,将对神经退行性疾病样本和细胞模型中PUFA早期氧化产物的存在情况进行检测。具有异常构象的蛋白质的积累被认为会通过干扰蛋白水解和线粒体功能而导致神经元死亡。还将讨论脂质过氧化物和脂质衍生醛加合物蛋白在脑衰老和与年龄相关的神经退行性变中的作用。