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Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer's disease

Dumont, Magali ; Wille, Elizabeth ; Calingasan, Noel Y. ; Tampellini, Davide LU ; Williams, Charlotte ; Gouras, Gunnar K. LU orcid ; Liby, Karen ; Sporn, Michael ; Flint Beal, M. and Lin, Michael T. (2009) In Journal of Neurochemistry 109(2). p.502-512
Abstract

Oxidative stress is one of the earliest events in the pathogenesis of Alzheimer's disease (AD) and can markedly exacerbate amyloid pathology. Modulation of antioxidant and anti-inflammatory pathways represents an important approach for AD therapy. Synthetic triterpenoids have been found to facilitate antioxidant response and reduce inflammation in several models. We investigated the effect of the triterpenoid, 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic acid-MethylAmide (CDDO-MA) in Tg19959 mice, which carry the human amyloid precursor protein with two mutations. These mice develop memory impairments and amyloid plaques as early as 2-3 months of age. CDDO-MA was provided with chow (800 mg/kg) from 1 to 4 months of age. CDDO-MA... (More)

Oxidative stress is one of the earliest events in the pathogenesis of Alzheimer's disease (AD) and can markedly exacerbate amyloid pathology. Modulation of antioxidant and anti-inflammatory pathways represents an important approach for AD therapy. Synthetic triterpenoids have been found to facilitate antioxidant response and reduce inflammation in several models. We investigated the effect of the triterpenoid, 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic acid-MethylAmide (CDDO-MA) in Tg19959 mice, which carry the human amyloid precursor protein with two mutations. These mice develop memory impairments and amyloid plaques as early as 2-3 months of age. CDDO-MA was provided with chow (800 mg/kg) from 1 to 4 months of age. CDDO-MA significantly improved spatial memory retention and reduced plaque burden, Aβ42 levels, microgliosis, and oxidative stress in Tg19959 mice.

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author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, Amyloid, Antioxidant, Memory, Oxidative stress, Triterpenoid
in
Journal of Neurochemistry
volume
109
issue
2
pages
502 - 512
publisher
Wiley-Blackwell
external identifiers
  • pmid:19200343
  • scopus:62649115489
ISSN
0022-3042
DOI
10.1111/j.1471-4159.2009.05970.x
language
English
LU publication?
no
id
a843c90a-3d0a-41a2-933a-7da3809518d8
date added to LUP
2020-02-27 11:13:03
date last changed
2024-01-02 06:34:50
@article{a843c90a-3d0a-41a2-933a-7da3809518d8,
  abstract     = {{<p>Oxidative stress is one of the earliest events in the pathogenesis of Alzheimer's disease (AD) and can markedly exacerbate amyloid pathology. Modulation of antioxidant and anti-inflammatory pathways represents an important approach for AD therapy. Synthetic triterpenoids have been found to facilitate antioxidant response and reduce inflammation in several models. We investigated the effect of the triterpenoid, 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic acid-MethylAmide (CDDO-MA) in Tg19959 mice, which carry the human amyloid precursor protein with two mutations. These mice develop memory impairments and amyloid plaques as early as 2-3 months of age. CDDO-MA was provided with chow (800 mg/kg) from 1 to 4 months of age. CDDO-MA significantly improved spatial memory retention and reduced plaque burden, Aβ42 levels, microgliosis, and oxidative stress in Tg19959 mice.</p>}},
  author       = {{Dumont, Magali and Wille, Elizabeth and Calingasan, Noel Y. and Tampellini, Davide and Williams, Charlotte and Gouras, Gunnar K. and Liby, Karen and Sporn, Michael and Flint Beal, M. and Lin, Michael T.}},
  issn         = {{0022-3042}},
  keywords     = {{Alzheimer's disease; Amyloid; Antioxidant; Memory; Oxidative stress; Triterpenoid}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{502--512}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Neurochemistry}},
  title        = {{Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1111/j.1471-4159.2009.05970.x}},
  doi          = {{10.1111/j.1471-4159.2009.05970.x}},
  volume       = {{109}},
  year         = {{2009}},
}