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.
Hashimoto
M
M
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
Rockenstein
E
E
Mante
M
M
Mallory
M
M
Masliah
E
E
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D019281:Dimerization; D015870:Gene Expression; D006801:Humans; D007163:Immunosorbent Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D011994:Recombinant Proteins / Q000378:metabolism; D051843:Synucleins; D014162:Transfection; D051844:alpha-Synuclein; D051846:beta-Synuclein
D000978:Antiparkinson Agents; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C497604:SNCA protein, human; C497607:SNCB protein, human; C497605:Snca protein, mouse; C497608:Sncb protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein