Coordination and redox properties of copper interaction with α-synuclein.
Parkinson's disease (PD) is a severe neurodegenerative disorder affecting movements. After Alzheimer's disease, it is the most common form of neurodegeneration. PD is characterized by the loss of neurons producing dopamine and by the presence of protein aggregates in the brain, known as Lewy bodies. The main constituent of Lewy bodies is the misfolded form of α-synuclein (αSyn), able to form oligomers and fibrils. In addition to protein aggregation, brain damage induced by oxidative stress, is also a frequent phenomenon in PD. αSyn is able to bind Copper ions in both Cu(II) and Cu(I) oxidation states. The metal binding is also maintained when αSyn interacts with membranes. Interestingly, copper binding to αSyn has strong impact either in protein misfolding or in free radical formation, such to provide a link between protein aggregation and oxidative damage. In this review the role of copper and αSyn in PD is discussed with a particular emphasis to elucidate (i) the interaction between copper and αSyn; (ii) the reactivity and (iii) potential toxicity associated with copper-αSyn complexes.
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy. Electronic address: daniela.valensin@unisi.it.
Daniela
D
Valensin
Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy.
Simone
S
Dell'Acqua
Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50383 Wroclaw, Poland.
Henryk
H
Kozlowski
Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy. Electronic address: luigi.casella@unipv.it.
Luigi
L
Casella
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003300:Copper / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
C497604:SNCA protein, human; D051844:alpha-Synuclein; D003300:Copper
Coordination sphere; Copper; Parkinson disease; Redox activity; Toxicity