Liu Xuebo, Yamada Naruomi, Osawa Toshihiko
The Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Science, Nagoya University, Nagoya, 464-8601, Japan,
Subcell Biochem. 2014;77:49-60. doi: 10.1007/978-94-007-7920-4_4.
Dopamine is the endogenous neurotransmitter produced by nigral neurons. Dopamine loss can trigger not only prominent secondary morphological changes, but also changes in the density and sensitivity of dopamine receptors; therefore, it is a sign of PD development. The reasons for dopamine loss are attributed to dopamine's molecular instability due to it is a member of catecholamine family, whose catechol structure contributes to high oxidative stress through enzymatic and non-enzymatic oxidation. Oxidative stress in the brain easily leads to the lipid peroxidation reaction due to a high concentration of polyunsaturated fatty acids (PUFA), such as docosahexaenoic acid (DHA, C22:6/ω-3) and arachidonic acid (AA, C18:4/ω-6). Recent studies have shown that lipid hydroperoxides, the primary peroxidative products, could non-specifically react with primary amino groups to form N-acyl-type (amide-linkage) adducts. Therefore, based on the NH2-teminals in dopamine's structure, the aims of this chapter are to describes the possibility that reactive LOOH species derived from DHA/AA lipid peroxidation may modify dopamine to form amide-linkage dopamine adducts, which might be related to etiology of Parkinson's diseases.
多巴胺是黑质神经元产生的内源性神经递质。多巴胺的丧失不仅会引发显著的继发性形态学变化,还会导致多巴胺受体密度和敏感性的改变;因此,这是帕金森病发展的一个标志。多巴胺丧失的原因归因于其作为儿茶酚胺家族成员的分子不稳定性,儿茶酚结构通过酶促和非酶促氧化导致高氧化应激。由于大脑中高浓度的多不饱和脂肪酸(PUFA),如二十二碳六烯酸(DHA,C22:6/ω-3)和花生四烯酸(AA,C18:4/ω-6),大脑中的氧化应激很容易导致脂质过氧化反应。最近的研究表明,脂质氢过氧化物作为主要的过氧化产物,可与伯氨基发生非特异性反应形成N-酰基型(酰胺键)加合物。因此,基于多巴胺结构中的NH2末端,本章的目的是描述源自DHA/AA脂质过氧化的活性LOOH物种可能修饰多巴胺形成酰胺键多巴胺加合物的可能性,这可能与帕金森病的病因有关。