The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human beta-amyloid precursor protein transgenic mice.
Metals such as zinc, copper and iron contribute to aggregation of amyloid-beta (Abeta) protein and deposition of amyloid plaques in Alzheimer's disease (AD). We examined whether the lipophilic metal chelator DP-109 inhibited these events in aged female hAbetaPP-transgenic Tg2576 mice. Daily gavage administration of DP-109 for 3 months markedly reduced the burden of amyloid plaques and the degree of cerebral amyloid angiopathy in brains, compared to animals receiving vehicle treatment. Moreover, DP-109 treatment appeared to facilitate the transition of Abeta from insoluble to soluble forms in the cerebrum. These results further support the hypothesis that endogenous metals are involved in the deposition of aggregated Abeta in brains of AD patients, and that metal chelators may be useful therapeutic agents in the treatment of AD.
Department of Neurology, National Creative Research Initiative Center for the Study of CNS Zinc, College of Medicine, University of Ulsan, Seoul 138-736, South Korea.
Joo-Yong
JY
Lee
Jonathan E
JE
Friedman
Itzchak
I
Angel
Alex
A
Kozak
Jae-Young
JY
Koh
D000375:Aging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002614:Chelating Agents / Q000008:administration & dosage; D004195:Disease Models, Animal; D004533:Egtazic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008670:Metals / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000187:drug effects / Q000378:metabolism; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D011994:Recombinant Proteins / Q000378:metabolism; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002614:Chelating Agents; C428063:DP-109; D008670:Metals; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D004533:Egtazic Acid