Dusek Petr, Roos Per M, Litwin Tomasz, Schneider Susanne A, Flaten Trond Peder, Aaseth Jan
Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Czech Republic; Institute of Neuroradiology, University Medicine Göttingen, Göttingen, Germany.
Department of Neurology, Division of Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
J Trace Elem Med Biol. 2015;31:193-203. doi: 10.1016/j.jtemb.2014.05.007. Epub 2014 Jun 2.
Impaired cellular homeostasis of metals, particularly of Cu, Fe and Mn may trigger neurodegeneration through various mechanisms, notably induction of oxidative stress, promotion of α-synuclein aggregation and fibril formation, activation of microglial cells leading to inflammation and impaired production of metalloproteins. In this article we review available studies concerning Fe, Cu and Mn in Parkinson's disease and Wilson's disease. In Parkinson's disease local dysregulation of iron metabolism in the substantia nigra (SN) seems to be related to neurodegeneration with an increase in SN iron concentration, accompanied by decreased SN Cu and ceruloplasmin concentrations and increased free Cu concentrations and decreased ferroxidase activity in the cerebrospinal fluid. Available data in Wilson's disease suggest that substantial increases in CNS Cu concentrations persist for a long time during chelating treatment and that local accumulation of Fe in certain brain nuclei may occur during the course of the disease. Consequences for chelating treatment strategies are discussed.
金属，特别是铜、铁和锰的细胞内稳态受损，可能通过多种机制引发神经退行性变，尤其是诱导氧化应激、促进α-突触核蛋白聚集和纤维形成、激活小胶质细胞导致炎症以及金属蛋白产生受损。在本文中，我们综述了有关帕金森病和威尔逊病中铁、铜和锰的现有研究。在帕金森病中，黑质中铁代谢的局部失调似乎与神经退行性变有关，表现为黑质铁浓度增加，同时伴有黑质铜和铜蓝蛋白浓度降低、脑脊液中游离铜浓度增加以及铁氧化酶活性降低。威尔逊病的现有数据表明，在螯合治疗期间，中枢神经系统铜浓度会持续大幅升高很长时间，并且在疾病过程中某些脑核可能会出现铁的局部蓄积。本文还讨论了螯合治疗策略的后果。
