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 Zn 2+ in vitro, whereas it was not affected by the presence of Ca 2+ or Mg 2+ . Circular dichroism spectra confirmed that α‐synuclein underwent conformational change in the presence of Zn 2+ . 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.