PMID- 23764200
OWN - NLM
STAT- MEDLINE
DCOM- 20130920
LR  - 20211021
IS  - 1750-1326 (Electronic)
IS  - 1750-1326 (Linking)
VI  - 8
DP  - 2013 Jun 13
TI  - Treatment with bexarotene, a compound that increases apolipoprotein-E, provides 
      no cognitive benefit in mutant APP/PS1 mice.
PG  - 18
LID - 10.1186/1750-1326-8-18 [doi]
AB  - BACKGROUND: Though the precise cause(s) of Alzheimer's disease (AD) remain 
      unknown, there is strong evidence that decreased clearance of beta-amyloid (Abeta) from 
      the brain can contribute to the disease. Therapeutic strategies to promote 
      natural Abeta clearance mechanisms, such as the protein apolipoprotein-E (APOE), 
      hold promise for the treatment of AD. The amount of APOE in the brain is 
      regulated by nuclear receptors including retinoid X receptors (RXRs). Drugs that 
      activate RXRs, including bexarotene, can increase APOE and ABCA1 production, and 
      have been shown to decrease the Abeta burden and improve cognition in mouse models 
      of Abeta amyloidosis. Although recent bexarotene studies failed to replicate the 
      rapid clearance of Abeta from brains, behavioral and cognitive effects of this 
      compound remain controversial. FINDINGS: In efforts to clarify these behavioral 
      findings, mutant APP/PS1 mice were acutely dosed with bexarotene. While ABCA1 was 
      upregulated in mutant APP/PS1 mice treated with bexarotene, this drug failed to 
      attenuate Abeta plaques or cognitive deficits in these mice. CONCLUSIONS: We 
      recommend rigorous preclinical study to evaluate the mechanism and utility of 
      such a compound for AD therapy.
FAU - LaClair, Katherine D
AU  - LaClair KD
AD  - Department of Pathology, The Johns Hopkins University School of Medicine, 720 
      Rutland Avenue, Ross 558, Baltimore, MD 21205, USA.
FAU - Manaye, Kebreten F
AU  - Manaye KF
FAU - Lee, Dexter L
AU  - Lee DL
FAU - Allard, Joanne S
AU  - Allard JS
FAU - Savonenko, Alena V
AU  - Savonenko AV
FAU - Troncoso, Juan C
AU  - Troncoso JC
FAU - Wong, Philip C
AU  - Wong PC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130613
PL  - England
TA  - Mol Neurodegener
JT  - Molecular neurodegeneration
JID - 101266600
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Tetrahydronaphthalenes)
RN  - A61RXM4375 (Bexarotene)
SB  - IM
EIN - Mol Neurodegener. 2013;8:26
MH  - ATP Binding Cassette Transporter 1
MH  - ATP-Binding Cassette Transporters/*biosynthesis
MH  - Alzheimer Disease/metabolism/*pathology
MH  - Animals
MH  - Anticarcinogenic Agents/*pharmacology
MH  - Apolipoproteins E/biosynthesis
MH  - Behavior, Animal/drug effects
MH  - Bexarotene
MH  - Blotting, Western
MH  - Disease Models, Animal
MH  - Female
MH  - Male
MH  - Memory/drug effects
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Plaque, Amyloid/metabolism/*pathology
MH  - Tetrahydronaphthalenes/*pharmacology
PMC - PMC3693923
EDAT- 2013/06/15 06:00
MHDA- 2013/09/21 06:00
PMCR- 2013/06/13
CRDT- 2013/06/15 06:00
PHST- 2013/03/28 00:00 [received]
PHST- 2013/06/06 00:00 [accepted]
PHST- 2013/06/15 06:00 [entrez]
PHST- 2013/06/15 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
PHST- 2013/06/13 00:00 [pmc-release]
AID - #N/A [pii]
AID - 1750-1326-8-18 [pii]
AID - 10.1186/1750-1326-8-18 [doi]
PST - epublish
SO  - Mol Neurodegener. 2013 Jun 13;8:18. doi: 10.1186/1750-1326-8-18.