Nobiletin, a citrus flavonoid, improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of Alzheimer's disease (3XTg-AD)

Copyright © 2015 Elsevier B.V. All rights reserved..

Alzheimer's disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function. Increasing evidence indicates that the production and accumulation of amyloid β (Aβ), particularly soluble Aβ oligomers, is central to the pathogenesis of AD. Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, ameliorates learning and memory impairment in olfactory-bulbectomized mice, amyloid precursor protein transgenic mice, NMDA receptor antagonist-treated mice, and senescence-accelerated mouse prone 8. Here, we present evidence that this natural compound improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of AD (3XTg-AD) that progressively develops amyloid plaques, neurofibrillary tangles, and cognitive impairments. Treatment with nobiletin (30 mg/kg) for 3 months reversed the impairment of short-term memory and recognition memory in 3XTg-AD mice. Our ELISA analysis also showed that nobiletin reduced the levels of soluble Aβ1-40 in the brain of 3XTg-AD mice. Furthermore, nobiletin reduced ROS levels in the hippocampus of 3XTg-AD as well as wild-type mice. These results suggest that this natural compound has potential to become a novel drug for the treatment and prevention of AD.

Medienart:

E-Artikel

Erscheinungsjahr:

2015

Erschienen:

2015

Enthalten in:

Zur Gesamtaufnahme - volume:289

Enthalten in:

Behavioural brain research - 289(2015) vom: 01. Aug., Seite 69-77

Sprache:

Englisch

Beteiligte Personen:

Nakajima, Akira [VerfasserIn]
Aoyama, Yuki [VerfasserIn]
Shin, Eun-Joo [VerfasserIn]
Nam, Yunsung [VerfasserIn]
Kim, Hyoung-Chun [VerfasserIn]
Nagai, Taku [VerfasserIn]
Yokosuka, Akihito [VerfasserIn]
Mimaki, Yoshihiro [VerfasserIn]
Yokoi, Tsuyoshi [VerfasserIn]
Ohizumi, Yasushi [VerfasserIn]
Yamada, Kiyofumi [VerfasserIn]

Links:

Volltext

Themen:

3XTg-AD
Alzheimer's disease
Amyloid beta-Peptides
Amyloid beta-protein (1-40)
Amyloid beta-protein (1-42)
D65ILJ7WLY
Flavones
Journal Article
Memory
Nobiletin
Oxidative stress
Peptide Fragments
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 05.02.2016

Date Revised 10.12.2019

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.bbr.2015.04.028

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM248437062