Nov. 02, 2001

UCSD Researchers Suggest Naturally Occurring Molecules
May Alleviate Build-Up of Plaque in Parkinsonís Patients

Naturally occurring molecules called beta-synucleins (b-synucleins) may have the ability to halt the excessive build-up of plaque-like deposits, called Lewy bodies, that are found in the dying neuron cells of Parkinsonís disease patients, according to researchers in the University of California, San Diego (UCSD) School of Medicine.

Eliezar Masliah, M.D., UCSD professor of neurosciences and pathology.

In findings published recently in the journal Neuron, investigators in the lab of senior author Eliezer Masliah, M.D., professor of neurosciences and pathology, showed in mice that b-synuclein inhibits the Lewy body-producing activity of a cousin molecule called alpha-synuclein, which has been linked to abnormal accumulation of Lewy bodies characteristically seen in the brainís of Parkinsonís patients.

Although the mechanism by which b-synuclein works to block a-synuclein Lewy body-formation is unknown, Masliah and his colleagues noted that an imbalance in the ratio of a- to b-synuclein might render a-synuclein more prone to the plaque-like development.

In test tube studies, the research team added b-synuclein to a-synuclein protein that had formed aggregates, the abnormal Lewy body deposits. When b-synuclein was added, the aggregates untangled.

In studies with mice, the researchers first developed one group with over-expressed a-synuclein and another group with large amounts of b-synuclein. The a-synuclein mice developed Lewy bodies while the b-synuclein group did not.

When the researchers developed mice bred with higher amounts of b-synuclein, compared to a-synuclein (such as in normal individuals), the b-synuclein ameliorated the motor deficits, neurodegenerative alteration, and neuronal a-synuclein accumulation of Lewy bodies that had been seen in the a-synuclein mice.

In addition to Masliah, the research team included first author Makoto Hashimoto, M.D., Edward Rockenstein, B.S.; Michael Mante, B.S., and Margaret Mallory, B.S., all in the UCSD Departments of Neurosciences and Pathology.

The research was supported by grants from the National Institute of Health and the Michael J. Fox Foundation for Parkinsonís Research.

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