Fink’s group monitored fibrillization of α-synuclein with thioflavin-T in the presence of various concentrations of baicalein. They found fibrillization was inhibited after 45-hour incubation of 70µM α-synuclein with 20μM baicalein. Furthermore, baicalein had no effect when it was added to fibril seeds of α-synuclein, indicating that baicalein works prior to the nucleation step of fibrillization.

Baicalein was also added at different time points in the fibrillization process and monitored via thioflavin-T fluorescence and light scattering. In the preliminary stages of fibril assembly, baicalein was able to inhibit fibril formation completely. When baicalein was introduced at later time points, it blocked fibril assembly and even disaggregated the α-synuclein fibrils.

After treating fibrils for four hours with baicalein, Fink and Zhu found that the fibrils had disaggregated into oligomers. Atomic force microscopy revealed that these were globular as well as donut-shaped oligomers, about 32-45nm in diameter. This is intriguing because some scientists think that donut- or pore-shaped oligomers precede fibrillization (for a review, see Volles and Lansbury, 2003). Moreover, baicalein has been shown to inhibit lipid peroxidation; α-synuclein is also known to bind lipids.

Fink’s group also reported that this phenomenon was seen when Aβ fibrils are treated with baicalein. However, from what is currently understood about the toxicity of Aβ and amyloid oligomers generally, it does not seem as though disaggregating fibrils into oligomers is preferable. Amyloid fibrils have long been thought to contribute to neurotoxicity, but this idea is slowly being replaced by the notion that amyloid intermediates exert much of the toxicity. Fink and colleagues have yet to test the toxicity of the oligomers produced by this process (See also Lebeau et al., 2001). You can view abstracts mentioned in this story at the SfN/ScholarOne website.—Erene Mina is a Ph.D. student at University of California, Irvine.