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The Role of Metal Binding in the Amyotrophic Lateral Sclerosis-Related Aggregation of Copper-Zinc Superoxide Dismutase

Department of Biochemistry, Biophysics and General Pathology, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Author to whom correspondence should be addressed.
Molecules 2017, 22(9), 1429;
Received: 19 July 2017 / Revised: 22 August 2017 / Accepted: 27 August 2017 / Published: 29 August 2017
(This article belongs to the Special Issue Metallopeptides)
PDF [1024 KB, uploaded 29 August 2017]


Protein misfolding and conformational changes are common hallmarks in many neurodegenerative diseases involving formation and deposition of toxic protein aggregates. Although many players are involved in the in vivo protein aggregation, physiological factors such as labile metal ions within the cellular environment are likely to play a key role. In this review, we elucidate the role of metal binding in the aggregation process of copper-zinc superoxide dismutase (SOD1) associated to amyotrophic lateral sclerosis (ALS). SOD1 is an extremely stable Cu-Zn metalloprotein in which metal binding is crucial for folding, enzymatic activity and maintenance of the native conformation. Indeed, demetalation in SOD1 is known to induce misfolding and aggregation in physiological conditions in vitro suggesting that metal binding could play a key role in the pathological aggregation of SOD1. In addition, this study includes recent advances on the role of aberrant metal coordination in promoting SOD1 aggregation, highlighting the influence of metal ion homeostasis in pathologic aggregation processes. View Full-Text
Keywords: metals; protein misfolding; SOD1; neurodegeneration; amyloid aggregation metals; protein misfolding; SOD1; neurodegeneration; amyloid aggregation

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Sirangelo, I.; Iannuzzi, C. The Role of Metal Binding in the Amyotrophic Lateral Sclerosis-Related Aggregation of Copper-Zinc Superoxide Dismutase. Molecules 2017, 22, 1429.

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