Dopamine promotes α‐synuclein aggregation into SDS‐resistant soluble oligomers via a distinct folding pathway

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Abstract
SPECIFIC AIMSThe pathological hallmark of Parkinson’s disease (PD) is the loss of dopamine producing neurons in the substantia nigra and the formation of intraneuronal Lewy bodies. Aggregated α-synuclein (α-SN) protein is the major component of the Lewy body. The aim of this work is to determine whether DA modulates the behavior of α-SN by studying the effect of DA on α-SN oligomerization. This would provide an important link between these two PD-associated molecules.PRINCIPAL FINDINGS1. Dopamine promotes α-SN oligomerization into SDS-resistant soluble oligomeric speciesThe association of α-SN aggregates within dopaminergic neurons in PD prompted us to investigate the effect of DA on α-SN oligomerization. Incubating recombinant wild-type human α-SN (14 μM) with increasing concentrations of DA for up to 3.5 h caused a time- and dose-dependent increase in SDS-resistant α-SN oligomers. DA mediated α-SN oligomers are rapidly formed and were readily detected after only 5 min with both 100 and 200 μM DA. While ...
Funding Information
  • National Health and Medical Research Council