Evidence map›Paper›PMID 30514854›Full record

ArticleScientific reports2018

A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model.

Jesus Campagna, Patricia Spilman, Barbara Jagodzinska, Dongsheng Bai, Asa Hatami, Chunni Zhu, Tina Bilousova, Michael Jun, Chris Jean Elias, Johnny Pham and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.6field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 36 citations in OpenAlex.

  1. SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  18. Olfactory impairment in men and mice related to aging and amyloid-induced pathology.Pflugers Archiv : European journal of physiology · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Jesus CampagnaThe Drug Discovery Lab, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Patricia SpilmanThe Drug Discovery Lab, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Barbara JagodzinskaThe Drug Discovery Lab, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Dongsheng BaiThe Drug Discovery Lab, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Asa HatamiThe Drug Discovery Lab, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Chunni ZhuThe Drug Discovery Lab, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Tina BilousovaThe Drug Discovery Lab, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Michael JunThe Drug Discovery Lab, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Chris Jean EliasThe Drug Discovery Lab, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Johnny PhamDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA.
Gregory ColeMary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Mary Jo LaDuDepartment of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois, 60612, USA.
Michael E JungDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA.
Dale E BredesenDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Varghese JohnThe Drug Discovery Lab, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. vjohn@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of Illinois Chicago · US

Funding

ApoE4-targeted therapeutics that normalize SirT1R01AG051386 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JOHN, VARGHESE · 2015 to 2019
$3.0M
NIA NIH HHS R01 AG051386U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG051386
6 · The paper itself

Abstract

We describe here the results from the testing of a small molecule first-in-class apolipoprotein E4 (ApoE4)-targeted sirtuin1 (SirT1) enhancer, A03, that increases the levels of the neuroprotective enzyme SirT1 while not affecting levels of neurotoxic sirtuin 2 (SirT2) in vitro in ApoE4-transfected cells. A03 was identified by high-throughput screening (HTS) and found to be orally bioavailable and brain penetrant. In vivo, A03 treatment increased SirT1 levels in the hippocampus of 5XFAD-ApoE4 (E4FAD) Alzheimer's disease (AD) model mice and elicited cognitive improvement while inducing no observed toxicity. We were able to resolve the enantiomers of A03 and show using in vitro models that the L-enantiomer was more potent than the corresponding D-enantiomer in increasing SirT1 levels. ApoE4 expression has been shown to decrease the level of the NAD-dependent deacetylase and major longevity determinant SirT1 in brain tissue and serum of AD patients as compared to normal controls. A deficiency in SirT1 level has been recently implicated in increased tau acetylation, a dominant post-translational modification and key pathological event in AD and tauopathies. Therefore, as a novel approach to therapeutic development for AD, we targeted identification of compounds that enhance and normalize brain SirT1 levels.

Indexed as

Alzheimer DiseaseAnimalsAntiparkinson AgentsApolipoprotein E4Cell Line, TumorDisease Models, AnimalHippocampusMiceMice, TransgenicSelective Serotonin Reuptake InhibitorsSirtuin 1Sirtuin 2Antiparkinson AgentsApolipoprotein E4Selective Serotonin Reuptake InhibitorsSirt1 protein, mouseSirt2 protein, mouseSirtuin 1Sirtuin 2

Identifiers

PMID30514854
PMCPMC6279743
OpenAlexW2902400140

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.