P4‐055: Attenuation of beta‐amyloid‐induced activation of astrocytes by curcumin: Role of protein SUMOylation

domains prevent fibril formation of Ab 40 and A b 42 far below stoichiometric ratio. Kinetic experiments show that BRICHOS prolongs the lag time for fibrillation and the effects on the elongation phase are more prominent for Ab 42 than for A b 40 (Fig. 1). The inhibitory effect is concentration dependent in a quantitative and highly reproducible manner. An ongoing aggregation process is retarded if BRICHOS is added at any time during the lag phase. Circular dichroism spectroscopy and analytical size exclusion chromatography imply that a main fraction of Ab is maintained as unstructured monomer during the extended lag phase in the presence of BRICHOS. Structural BRICHOS models display a conserved array of tyrosine rings on a five-stranded b-sheet, with inter-hydroxyl distances suited for hydrogen bonding peptides in extended b-conformation. This array is lined with more charged residues in Bri2 than in proSP-C. Conclusions: Our data imply that the inhibitory mechanism is reliant on BRICHOS interfering with processes involving aggregated species, most likely fibril-dependent secondary nucleation, which is a major determinant of the length of the lag phase and the sharpness of the kinetic transition for Ab.