The correlation between neurotoxicity, aggregative ability and secondary structure studied by sequence truncated Abeta peptides.
Aggregated beta-amyloid (Abeta) peptides are neurotoxic and cause neuronal death both in vitro and in vivo. Although the formation of a beta-sheet structure is usual required to form aggregates, the relationship between neurotoxicity and the Abeta sequence remains unclear. To explore the correlation between Abeta sequence, secondary structure, aggregative ability, and neurotoxicity, we utilized both full-length and fragment-truncated Abeta 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 Abeta peptide, (e.g. Abeta17-35), does not display the neurotoxicity of either full-length or 17-21, 25-35 truncated Abeta peptides.
Liao
M Q
MQ
Institute of Molecular and Cellular Biology, Tzu Chi University, Hualien 970, Taiwan.
Tzeng
Y J
YJ
Chang
Lea Y X
LY
Huang
H B
HB
Lin
T H
TH
Chyan
C L
CL
Chen
Y C
YC
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D019281:Dimerization; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000209:etiology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D051381:Rats; D017384:Sequence Deletion
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments