A hallmark of these disorders is the presence of aggregates of specific proteins in the brains of patients.

If we could find a way to interfere with the formation of these aggregates, or to destroy them once they are formed, we might be able to eradicate or ameliorate these conditions.

This is exactly what Dr. Eliever Masliah of the University of California San Diego and colleagues have achieved in a mouse model of Parkinson's disease. Their results are reported in today's issue of Neuron.

Mutations in the gene alpha-synuclein are associated with a rare form of inherited Parkinson's Disease. The alpha-synuclein protein has been shown to form clumps or aggregates, similar to those found in the neurons of Parkinson's patients.

Several proteins related to alpha-synuclein have also been identified, but interestingly, while relatives (called beta-synucleins) can bind to alpha-synuclein, they do not form aggregates on their own and can block the ability of alpha-synuclein to form aggregates.

Dr. Masliah and colleagues reasoned that if the non-clumping beta variant prevented the clumping of alpha-synuclein, perhaps it would also be able to block the formation of aggregates in the brain and ultimately prevent neurodegeneration.

The researchers made mice that produced high levels of the clumping form of alpha-synuclein and found that the mice had both a brain pathology similar to Parkinson's patients and difficulty with motor coordination and balance.

Strikingly, mice that produced high levels of both the clumping form of alpha-synuclein and non-clumping form of beta-synuclein seemed more normal: their neurons showed diminished signs of disease and their coordination and balance was improved.

While the mechanism by which the related beta-synuclein protein interferes with aggregate formation is not entirely clear, these results suggest a novel strategy for the treatment of neurodegenerative disorders.

Perhaps in the future, the beta-synuclein protein, or others with similar properties, may be delivered to patients to reduce or prevent the development of these detrimental aggregates in neurons.

[Contact: Eliezer Masliah]

25-Oct-2001