Molecular Physiology and Biophysics Unit, Department of Biology, Università di Padova, 35131 Padova, Italy.
Biomolecules. 2020 Jan 29;10(2):195. doi: 10.3390/biom10020195.
The involvement of copper in numerous physiological processes makes this metal ion essential for human life. Alterations in copper homeostasis might have deleterious consequences, and several neurodegenerative disorders, including Parkinson's disease (PD), have been associated with impaired copper levels. In the present review, we describe the molecular mechanisms through which copper can exert its toxicity, by considering how it can interfere with other cellular processes known to play a role in PD, such as dopamine metabolism, oxidative stress, and α-synuclein aggregation. The recent experimental evidence that associates copper deficiency and the formation of superoxide dismutase 1 (SOD1) aggregates with the progression of PD is also discussed together with its therapeutic implication. Overall, the recent discoveries described in this review show how either copper deficiency or excessive levels can promote detrimental effects, highlighting the importance of preserving copper homeostasis and opening unexplored therapeutic avenues in the definition of novel disease-modifying drugs.
铜在许多生理过程中的参与使这种金属离子对人类生命至关重要。铜稳态的改变可能产生有害的后果，并且几种神经退行性疾病，包括帕金森病（PD），与铜水平降低有关。在本综述中，我们描述了铜可以通过干扰已知在 PD 中起作用的其他细胞过程（如多巴胺代谢、氧化应激和α-突触核蛋白聚集）来发挥其毒性的分子机制。还讨论了最近的实验证据，该证据将铜缺乏症和超氧化物歧化酶 1（SOD1）聚集体的形成与 PD 的进展联系起来，并讨论了其治疗意义。总的来说，本综述中描述的最新发现表明，铜缺乏症或铜含量过高都会促进有害影响，突出了维持铜稳态的重要性，并为定义新的疾病修饰药物开辟了尚未探索的治疗途径。
