Structural changes in α-synuclein affect its chaperone-like activity in vitro



α-Synuclein, a major constituent of Lewy bodies (LBs) in Parkinson's disease (PD), has been implicated to play a critical role in synaptic events, such as neuronal plasticity during development, learning, and degeneration under pathological conditions, although the physiological function of α-synuclein has not yet been established. We here present biochemical evidence that recombinant α-synuclein has a chaperone-like function against thermal and chemical stress in vitro. In our experiments, α-synuclein protected glutathione S-transferase (GST) and aldolase from heat-induced precipitation, and α-lactalbumin and bovine serum albumin from dithiothreitol (DTT)-induced precipitation like other molecular chaperones. Moreover, preheating of α-synuclein, which is believed to reorganize the molecular surface of α-synuclein, increased the chaperone-like activity. Interestingly, in organic solvents, which promotes the formation of secondary structure, α-synuclein aggregated more easily than in its native condition, which eventually might abrogate the chaperone-like function of the protein. In addition, α-synuclien was also rapidly and significantly precipitated by heat in the presence of Zn2+ in vitro, whereas it was not affected by the presence of Ca2+ or Mg2+. Circular dichroism spectra confirmed that α-synuclein underwent conformational change in the presence of Zn2+. Taken together, our data suggest that α-synuclein could act as a molecular chaperone, and that the conformational change of the α-synuclein could explain the aggregation kinetics of α-synuclein, which may be related to the abolishment of the chaperonic-like activity.