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-synuclein 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.