Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer's disease.
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, Abeta42 levels, microgliosis, and oxidative stress in Tg19959 mice.
Dumont
Magali
M
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York 10065, USA. mad2138@med.cornell.edu
Wille
Elizabeth
E
Calingasan
Noel Y
NY
Tampellini
Davide
D
Williams
Charlotte
C
Gouras
Gunnar K
GK
Liby
Karen
K
Sporn
Michael
M
Nathan
Carl
C
Flint Beal
M
M
Lin
Michael T
MT
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000473:pathology; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*
C530803:2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl amide; D014315:Triterpenes; D009828:Oleanolic Acid