Interaction between alpha-synuclein and metal ions, still looking for a role in the pathogenesis of Parkinson's disease.
The most recent literature on the interaction between alpha-synuclein in its several aggregation states and metal ions is discussed. This analysis shows two major types of interactions. Binding sites are present in the C-terminal region, and similar, low affinity (in the millimolar range) is exhibited toward many different metal ions, including copper and iron. A more complex scenario emerges for these latter metal ions, which are also able to coordinate with high affinity (in the micromolar range) to the N-terminal region of alpha-synuclein. Moreover, these redox-active metal ions may induce chemical modifications on the protein in vitro and in the reducing intracellular environment, and these modifications might be relevant for the aggregation properties of alpha-synuclein. Finally, an attempt is made to contextualize the interaction between alpha-synuclein and these metal ions in the framework of the elusive and multifactorial pathogenesis of Parkinson's disease.
Bisaglia
Marco
M
Department of Biology, University of Padova, Via U. Bassi 58/B, 35121, Padova, Italy.
Tessari
Isabella
I
Mammi
Stefano
S
Bubacco
Luigi
L
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism; D008670:Metals / Q000378:metabolism* / Q000633:toxicity; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D051844:alpha-Synuclein / Q000378:metabolism*
D008670:Metals; C497604:SNCA protein, human; D051844:alpha-Synuclein