α-synuclein is one of the major proteins found in Lewy bodies (LBs), the cytoplasmic inclusions that pepper the neurons of patients suffering from one of several neurodegenerative diseases, including Parkinson's, Alzheimer's, and dementia with Lewy bodies. Whether LBs are protective or damaging is widely debated, as is the sequence of events that leads to the aggregation of α-synuclein itself. New evidence, presented in the October 25 Neuron, suggests that aggregation may, in part, be controlled by β-synuclein.

Researchers from Eliezer Masliah's lab at University of California, San Diego, report that β-synuclein can prevent, and even reverse, the aggregation of the α-isoform. Their evidence comes from in vivo, cell culture, and biochemical experiments. Transgenic mice expressing human α-synuclein exhibited signs of neurodegeneration; a loss of dopaminergic nerve terminals, the presence of inclusion bodies, and loss of locomotor activity. Double transgenics expressing both α- and β-synuclein, however, had close to normal locomotor activity, four-fold fewer inclusion bodies, and wildtype levels of dopaminergic terminals. In addition, α- and β-isoforms co-immunoprecipitated from bitransgenic tissues and from cultured cells coexpressing both isoforms, while in vitro the addition of β-synuclein to α-synuclein aggregates converted most of the α form to monomers.

"This paper is very helpful to the field," says Michael Schlossmacher, at Brigham and Women's Hospital, Boston. "It reports a strong behavioral and morphological modulation, and the coexpression of β-synuclein certainly seems to ameliorate the phenotype."-Tom Fagan.
References: Hashimoto M, Rockenstein E, Mante M, Mallory M, Masliah E. b-synuclein inhibits a-synuclein aggregation: A possible role as an anti-Parkinsonian factor. Neuron 2001 October 25;(32):213-223. Abstract

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References

Paper Citations

  1. . beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor. Neuron. 2001 Oct 25;32(2):213-23. PubMed.

External Citations

  1. BioMedNet
  2. See related UniSci story

Further Reading

Papers

  1. . beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor. Neuron. 2001 Oct 25;32(2):213-23. PubMed.

Primary Papers

  1. . beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor. Neuron. 2001 Oct 25;32(2):213-23. PubMed.