Chrysamine G and its derivative reduce amyloid beta-induced neurotoxicity in mice.
The neurotoxicity of amyloid beta (Abeta) is widely believed to play a seminal role in neurodegeneration in Alzheimer's disease. We examined the effect of Chrysamine G (CG) on such neurotoxicity using the specific measurement of surviving neurons. CG was found to reduce the neurodegeneration induced by both the active short fragment of Abeta(25-35) and full-sized Abeta(1-40). In this study, we synthesized a new chemical compound from a monovalent structure of CG (hCG), with a lower affinity for Abeta, and compared its activity with that of CG. Both CG and hCG were found to be equally efficacious in reducing Abeta-induced neuronal death at a concentration of 0.1-1 microM, indicating that the mechanism of action for CG was not due to its chelating activity, but rather due to its anti-oxidant activity.
Ishii
Kazuhiro
K
Department of Molecular Biology, Tokyo Institute of Psychiatry, Kamikitazawa, Tokyo 156-8585, Japan.
Klunk
William E
WE
Arawaka
Shigeki
S
Debnath
Manik L
ML
Furiya
Yoshiko
Y
Sahara
Naruhiko
N
Shoji
Shin'ichi
S
Tamaoka
Akira
A
Pettegrew
Jay W
JW
Mori
Hiroshi
H
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004622:Embryo, Mammalian; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D001565:Benzoates; D001713:Biphenyl Compounds; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); C092559:chrysamine G