Montine T J, Amarnath V, Martin M E, Strittmatter W J, Graham D G
Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
Am J Pathol. 1996 Jan;148(1):89-93.
Lipid peroxidation increases with age in brain and is elevated further in Alzheimer's disease. E-4-hydroxy-2-nonenal and malondialdehyde are products of lipid peroxidation that can adduct and cross-link protein. Neurofibrillary tangles, a feature of Alzheimer's disease composed mostly of tau protein, contain cross-linked and ubiquitin-conjugated protein. In P19 neuroglial cultures, E-4-hydroxy-2-nonenal was a potent cytotoxin that cross-linked cytoskeletal proteins, including tau into high molecular weight species that were conjugated with ubiquitin. Malondialdehyde formed monoadducts with cell protein but did not cross-link and was not cytotoxic. A non-crosslinking analogue of E-4-hydroxy-2-nonenal was not cytotoxic. E-4-Hydroxy-2-nonenal may contribute to neurodegeneration and neurofibrillary tangle formation in Alzheimer's disease.
脂质过氧化在大脑中随年龄增长而增加，在阿尔茨海默病中进一步升高。E-4-羟基-2-壬烯醛和丙二醛是脂质过氧化的产物，它们可以与蛋白质加合和交联。神经原纤维缠结是阿尔茨海默病的一个特征，主要由tau蛋白组成，其中含有交联和泛素结合的蛋白质。在P19神经胶质细胞培养物中，E-4-羟基-2-壬烯醛是一种强效细胞毒素，它能将包括tau蛋白在内的细胞骨架蛋白交联成与泛素结合的高分子量物质。丙二醛与细胞蛋白形成单加合物，但不发生交联，也没有细胞毒性。E-4-羟基-2-壬烯醛的一种非交联类似物没有细胞毒性。E-4-羟基-2-壬烯醛可能在阿尔茨海默病的神经退行性变和神经原纤维缠结形成中起作用。
