β-Synuclein Inhibits α-Synuclein Aggregation
2001; Cell Press; Volume: 32; Issue: 2 Linguagem: Inglês
10.1016/s0896-6273(01)00462-7
ISSN1097-4199
AutoresMakoto Hashimoto, Edward Rockenstein, Michael Mante, Margaret Mallory, Eliezer Masliah,
Tópico(s)Neurological disorders and treatments
ResumoAbstract We characterized β-synuclein, the non-amyloidogenic homolog of α-synuclein, as an inhibitor of aggregation of α-synuclein, a molecule implicated in Parkinson's disease. For this, doubly transgenic mice expressing human (h) α- and β-synuclein were generated. In doubly transgenic mice, β-synuclein ameliorated motor deficits, neurodegenerative alterations, and neuronal α-synuclein accumulation seen in hα-synuclein transgenic mice. Similarly, cell lines transfected with β-synuclein were resistant to α-synuclein accumulation. hα-synuclein was coimmunoprecipitated with hβ-synuclein in the brains of doubly transgenic mice and in the double-transfected cell lines. Our results raise the possibility that β-synuclein might be a natural negative regulator of α-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 β-synuclein might also provide a novel strategy for the treatment of neurodegenerative disorders.
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