The presence of α-synuclein (αSyn) -rich aggregates (Lewy bodies) in neurons of the substantia nigra is the defining histopathological hallmark of Parkinson's disease (PD). It has so far been reported that αSyn was an unfolded monomer without a specific structure. Recently, several studies suggested that αSyn produced in Escherichia coli or isolated from mammalian cells exists predominantly as a tetramer. I will present our data of αSyn proteins and brain analysis by small-angle X-ray (SAXS) at Spring-8 in Japan and neutron (SANS) scattering at The Institute Laue-Langevin (ILL) in France.
I also focus on the function of αsyn. Recent report showed that more than 90% of αSyn aggregates are present in the form of very small deposits in presynaptic terminals of the affected neurons in DLB. However, the mechanisms responsible for the presynaptic accumulation of abnormal αSyn remain unclear. I will review the recent findings on the involvement of presynaptic dysfunction in the initiation of neuronal dysfunctional changes including our data.