β-synuclein inhibits α-synuclein aggregation:: A possible role as an anti-parkinsonian factor

We characterized beta -synuclein, the non-amyloidogenic homolog of alpha -synuclein, as an inhibitor of aggregation of alpha -synuclein, a molecule implicated in Parkinson's disease. For this, doubly transgenic mice expressing human (h)alpha- and beta -synuclein were generated. In doubly transgenic mice, beta -synuclein ameliorated motor deficits, neurodegenerative alterations, and neuronal alpha -synuclein accumulation seen in h alpha -synuclein transgenic mice. Similarly, cell lines transfected with beta -synuclein were resistant to alpha -synuclein accumulation. h alpha -synuclein was coimmunoprecipitated with h beta -synuclein in the brains of doubly transgenic mice and in the double-transfected cell lines. Our results raise the possibility that beta -synuclein might be a natural negative regulator of alpha -synuclein aggregation and that a similar class of endogenous factors might regulate the aggregation state of other molecules involved in neurodegeneration. Such an anti-amyloidogenic property of beta -synuclein might also provide a novel strategy for the treatment of neurodegenerative disorders.