Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC), Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, Rosario, Argentina.
Department of Chemistry, Center for Research and Advanced Studies (Cinvestav), Mexico City, Mexico.
J Neurochem. 2019 Sep;150(5):507-521. doi: 10.1111/jnc.14721. Epub 2019 Jul 9.
Parkinson's disease is the second most common neurodegenerative disorder worldwide. Neurodegeneration in this pathology is characterized by the loss of dopaminergic neurons in the substantia nigra, coupled with cytoplasmic inclusions known as Lewy bodies containing α-synuclein. The brain is an organ that concentrates metal ions, and there is emerging evidence that a break-down in metal homeostasis may be a critical factor in a variety of neurodegenerative diseases. α-synuclein has emerged as an important metal-binding protein in the brain, whereas these interactions play an important role in its aggregation and might represent a link between protein aggregation, oxidative damage, and neuronal cell loss. Additionally, α-synuclein undergoes several post-translational modifications that regulate its structure and physiological function, and may be linked to the aggregation and/or oligomer formation. This review is focused on the interaction of this protein with physiologically relevant metal ions, highlighting the cases where metal-AS interactions profile as key modulators for its structural, aggregation, and membrane-binding properties. The impact of α-synuclein phosphorylation and N-terminal acetylation in the metal-binding properties of the protein are also discussed, underscoring a potential interplay between PTMs and metal ion binding in regulating α-synuclein physiological functions and its role in pathology. This article is part of the Special Issue "Synuclein".
帕金森病是全球第二常见的神经退行性疾病。该病理学中的神经退行性变的特征是黑质中多巴胺能神经元的丧失，以及含有α-突触核蛋白的称为路易体的细胞质包含物。大脑是一种集中金属离子的器官，有新的证据表明，金属内稳态的破坏可能是各种神经退行性疾病的一个关键因素。α-突触核蛋白已成为大脑中一种重要的金属结合蛋白，而这些相互作用在其聚集过程中起着重要作用，并可能代表蛋白聚集、氧化损伤和神经元细胞丢失之间的联系。此外，α-突触核蛋白经历了几种翻译后修饰，这些修饰调节其结构和生理功能，并且可能与聚集和/或寡聚体形成有关。这篇综述的重点是该蛋白与生理相关的金属离子的相互作用，强调了金属-AS 相互作用作为其结构、聚集和膜结合特性的关键调节剂的情况。还讨论了蛋白中α-突触核蛋白磷酸化和 N 端乙酰化对金属结合特性的影响，强调了 PTMs 和金属离子结合在调节α-突触核蛋白生理功能及其在病理学中的作用之间的潜在相互作用。本文是“突触核蛋白”特刊的一部分。
