Münch G, Lüth H J, Wong A, Arendt T, Hirsch E, Ravid R, Riederer P
Neuroimmunological Cell Biology Group, Interdisciplinary Center for Clinical Research (IZKF), University of Leipzig, Leipzig, Germany.
J Chem Neuroanat. 2000 Dec;20(3-4):253-7. doi: 10.1016/s0891-0618(00)00096-x.
An excess of reactive carbonyl compounds (carbonyl stress) and their reaction products, advanced glycation endproducts (AGEs), are thought to play a decisive role in the pathogenesis of neurodegenerative disorders and Parkinson's disease (PD) in particular. Accumulation of AGEs in various intracellular pathological hallmarks of PD, such as Lewy bodies, densely crosslinked intracellular protein deposits formed from neurofilament components and alpha-synuclein, have already been described in patients in advanced stages of the disease. There is, however, no indication of the involvement of AGE-induced crosslinking of alpha-synuclein in very early stages of the disease. In this study, we observed that AGEs and alpha-synuclein are similarly distributed in very early Lewy bodies in the human brain in cases with incidental Lewy body disease. These cases might be viewed as pre-Parkinson patients, i.e. patients who came for autopsy before the possible development of clinical signs of PD. AGEs are both markers of transition metal induced oxidative stress as well as, inducers of protein crosslinking and free radical formation by chemical and cellular processes. Thus, it is likely that AGE promoted formation of Lewy bodies reflects very early causative changes rather than late epiphenomenons of PD.
过量的活性羰基化合物（羰基应激）及其反应产物——晚期糖基化终产物（AGEs），被认为在神经退行性疾病的发病机制中起决定性作用，尤其是在帕金森病（PD）中。在疾病晚期患者中，已经发现AGEs在PD的各种细胞内病理特征中积累，如路易小体，它是由神经丝成分和α-突触核蛋白形成的密集交联的细胞内蛋白质沉积物。然而，在疾病的极早期阶段，没有迹象表明AGE诱导的α-突触核蛋白交联参与其中。在本研究中，我们观察到在伴有偶然性路易小体病的人类大脑极早期路易小体中，AGEs和α-突触核蛋白的分布相似。这些病例可被视为帕金森病前期患者，即在可能出现PD临床症状之前接受尸检的患者。AGEs既是过渡金属诱导的氧化应激的标志物，也是通过化学和细胞过程诱导蛋白质交联和自由基形成的诱导剂。因此，AGE促进路易小体形成很可能反映了PD极早期的致病变化，而不是晚期的附带现象。
