Aggregated b-amyloid (Ab) peptides are neurotoxic and cause neuronal death both in vitro and in vivo. Although the formation of a b-sheet structure is usual required to form aggregates, the relationship between neurotoxicity and the Ab sequence remains unclear. To explore the correlation between Ab sequence, secondary structure, aggregative ability, and neurotoxicity, we utilized both full-length and fragment-truncated Ab peptides. Using a combination of spectroscopic and cellular techniques, we demonstrated that neurotoxicity and aggregative ability are correlated while the relationship between these characteristics and secondary structure is not significant. The hydrophobic C-terminus, particularly the amino acids of 17-21, 25-35, and 41-42, is the main region responsible for neurotoxicity and aggregation. Deleting residues 17-21, 25-35 or 41-42 significantly reduced the toxicity. On the other hand, truncation of the peptides at either residues 22-24 or residues 36-40 had little effect on toxicity and aggregative ability. While the N-terminal residues 1-16 may not play a major role in neurotoxicity and aggregation, a lack of N-terminal fragment Ab peptide, (e.g. Ab17-35), does not display the neurotoxicity of either full-length or 17-21, 25-35 truncated Ab peptides.

Bisphenols (BPs) are widely used in the production of plastic material, misfolded human islet amyloid polypeptide (hIAPP) is a causal factor in diabetes. We demonstrated BPs analogues show different effects on hIAPP amyloid formation.

Bioactive isoliquiritigenin and liquiritin inhibit α-synuclein aggregation and extend the life span of the C. elegans model of Parkinson's disease.