beta-synuclein inhibits alpha-synuclein aggregation: A possible role as ananti-parkinsonian factor

We characterized beta -synuclein, the non-amyloidogenic homolog of alpha -s ynuclein, as an inhibitor of aggregation of alpha -synuclein, a molecule im plicated in Parkinson's disease. For this, doubly transgenic mice expressin g human (h)alpha- and beta -synuclein were generated. In doubly transgenic mice, beta -synuclein ameliorated motor deficits, neurodegenerative alterat ions, and neuronal alpha -synuclein accumulation seen in h alpha -synuclein transgenic mice. Similarly, cell lines transfected with beta -synuclein we re resistant to alpha -synuclein accumulation. h alpha -synuclein was coimm unoprecipitated with h beta -synuclein in the brains of doubly transgenic m ice and in the double-transfected cell lines. Our results raise the possibi lity that beta -synuclein might be a natural negative regulator of alpha -s ynuclein aggregation and that a similar class of endogenous factors might r egulate the aggregation state of other molecules involved in neurodegenerat ion. Such an anti-amyloidogenic property of beta -synuclein might also prov ide a novel strategy for the treatment of neurodegenerative disorders.