Comparative properties of Aβ1-42, Aβ11-42, and [Pyr¹¹]Aβ11-42 generated from O-acyl isopeptides.
The use of water-soluble O-acyl isopeptides enabled us to investigate the biochemical properties of Aβ11-42 species, by preparing highly concentrated stock solutions after a pretreatment. Aβ11-42 and [Pyr(11)]Aβ11-42 showed comparable aggregation capability and cytotoxicity, suggesting that the pyroglutamate modification at Glu(11) does not have a crucial role in these events. However, given that Aβ11-42 is converted to [Pyr(11)]Aβ11-42 by a glutamyl cyclase in vivo, the potential aggregative and cytotoxic nature of [Pyr(11)]Aβ11-42 that was observed in the present study provides valuable insights into the pathological functions of pyroglutamate-modified Aβ species in Alzheimer's disease.
Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan. ysohma@mol.f.u-tokyo.ac.jp
Youhei
Y
Sohma
Moe
M
Yamasaki
Hiroyuki
H
Kawashima
Atsuhiko
A
Taniguchi
Masayuki
M
Yamashita
Kenichi
K
Akaji
Hidehito
H
Mukai
Yoshiaki
Y
Kiso
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D006801:Humans; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments