beta-Synuclein inhibits alpha-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 ... halpha-synuclein transgenic mice. Similarly, cell lines transfected with beta-synuclein were resistant to alpha-synuclein accumulation. halpha-synuclein was coimmunoprecipitated with hbeta-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.
Mesh Terms:
Animals, Antiparkinson Agents, Brain, Dimerization, Gene Expression, Humans, Immunosorbent Techniques, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Motor Activity, Nerve Tissue Proteins, Neurodegenerative Diseases, Recombinant Proteins, Synucleins, Transfection, alpha-Synuclein, beta-Synuclein
Animals, Antiparkinson Agents, Brain, Dimerization, Gene Expression, Humans, Immunosorbent Techniques, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Motor Activity, Nerve Tissue Proteins, Neurodegenerative Diseases, Recombinant Proteins, Synucleins, Transfection, alpha-Synuclein, beta-Synuclein
Neuron
Date: Oct. 25, 2001
PubMed ID: 11683992
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