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beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor.

Abstract
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.
AuthorsM Hashimoto, E Rockenstein, M Mante, M Mallory, E Masliah
JournalNeuron (Neuron) Vol. 32 Issue 2 Pg. 213-23 (Oct 25 2001) ISSN: 0896-6273 [Print] United States
PMID11683992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antiparkinson Agents
  • Nerve Tissue Proteins
  • Recombinant Proteins
  • SNCA protein, human
  • SNCB protein, human
  • Snca protein, mouse
  • Sncb protein, mouse
  • Synucleins
  • alpha-Synuclein
  • beta-Synuclein
Topics
  • Animals
  • Antiparkinson Agents (pharmacology)
  • Brain (metabolism)
  • Dimerization
  • Gene Expression
  • Humans
  • Immunosorbent Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Motor Activity
  • Nerve Tissue Proteins (chemistry, genetics, metabolism, pharmacology, therapeutic use)
  • Neurodegenerative Diseases (drug therapy)
  • Recombinant Proteins (metabolism)
  • Synucleins
  • Transfection
  • alpha-Synuclein
  • beta-Synuclein

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