title: Curcumin derivative with the substitution at C-4 position, but not curcumin, is effective against amyloid pathology in APP/PS1 mice.
abstract: Recent evidence supports the amyloid cascade hypothesis that a pathological change of amyloid β (Aβ) in the brain is an initiating event in Alzheimer's disease (AD). Accordingly, modulating the abnormal Aβ aggregation is considered a potential therapeutic target in AD. Curcumin, a low-molecular-weight polyphenol derived from the well-known curry spice turmeric, has shown favorable effects on preventing or treating AD pathology. The present study investigated the effects of curcumin and 2 novel curcumin derivatives, FMeC1 and FMeC2, on AD pathology in APPswe/PS1dE9 double transgenic mice. Mice fed a chow diet that contained FMeC1 for 6 months showed a reduction in insoluble Aβ deposits and glial cell activity together with reduced cognitive deficits, compared to animals receiving a control diet or with curcumin or FMeC2 in their diet. Both curcumin and FMeC1 modulated the formation of Aβ aggregates; however, only FMeC1 significantly attenuated the cell toxicity of Aβ. These results indicate that FMeC1 may have potential for preventing AD.
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Yanagisawa
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Nor Faeizah
authors.initials: NF
authors.lastname: Ibrahim
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Taguchi
authors.affiliation: Department of Fundamental Nursing, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Morikawa
authors.affiliation: Northeastern Industrial Research Center of Shiga Prefecture, Nagahama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirao
authors.affiliation: Northeastern Industrial Research Center of Shiga Prefecture, Nagahama, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shirai
authors.affiliation: Otsuka Pharmaceutical Co., Ltd, Kawauchi-cho, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sogabe
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan. Electronic address: kinchan@belle.shiga-med.ac.jp.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tooyama
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003071:Cognition; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D009457:Neuroglia / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000235:genetics / Q000517:prevention & control
chemical_list: D016229:Amyloid beta-Peptides; D053764:Presenilin-1; C580804:presenilin 1, mouse; D003474:Curcumin
keywords: APP/PS1 transgenic mice; Alzheimer's disease; amyloid-β; curcumin