Evidence map›Paper›PMID 23264626›Full record

ArticleThe Journal of biological chemistry2013

Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice.

Qiu-Lan Ma, Xiaohong Zuo, Fusheng Yang, Oliver J Ubeda, Dana J Gant, Mher Alaverdyan, Edmond Teng, Shuxin Hu, Ping-Ping Chen, Panchanan Maiti and 3 more

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

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% 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

102 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.

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42 more citing papers are in PubMed but not listed here.

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

13 authors at 2 institutions in 2 countries.

Qiu-Lan MaDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, the Geriatric, Research, and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California 90073, USA.
Xiaohong Zuo
Fusheng Yang
Oliver J Ubeda
Dana J Gant
Mher Alaverdyan
Edmond Teng
Shuxin Hu
Ping-Ping Chen
Panchanan Maiti
Bruce Teter
Greg M Cole
Sally A Frautschy
University of California, Los Angeles · USVA Greater Los Angeles Healthcare System · US

Funding

UCLA ALZHEIMERS DISEASE RESEARCH CENTERP50AG016570 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BREDESEN, DALE E. · 1999 to 2014
$25.9M
UCLA OLDER AMERICANS INDEPENDENCE CENTERP30AG028748 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUBEN, DAVID B. · 2006 to 2017
$9.8M
Preclinical Pharmacogenomics and Synaptic Biomarkers for Alzheimer's DiseaseR01AT006816 · NCCIH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COLE, GREGORY M, FRAUTSCHY, SALLY ANN · 2011 to 2015
$1.9M
Human tau neurodegeneration in Alzheimer'sR01AG021975 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FRAUTSCHY, SALLY ANN · 2004 to 2008
$1.2M
Diet and Exercise (DE) Program for Alzheimer PreventionRC1AG035878 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COLE, GREGORY M, FRAUTSCHY, SALLY ANN · 2009 to 2010
$1.0M
Assessment of Biomarkers and Behavior in a Transgenic Rat Model of ADK08AG034628 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TENG, EDMOND HUATUNG · 2009 to 2013
$540k
NCCIH NIH HHS AT006816NCCIH NIH HHS R01 AT006816NIA NIH HHS K08 AG034628NIA NIH HHS K08 AG34628NIA NIH HHS P01 AG16570NIA NIH HHS P30 AG028748NIA NIH HHS P30-AG028748NIA NIH HHS P50 AG016570NIA NIH HHS R01 AG021975NIA NIH HHS RC1 AG035878
6 · The paper itself

Abstract

The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected.

Indexed as

AgedAged, 80 and overAnimalsAnti-Inflammatory Agents, Non-SteroidalBehavior, AnimalCurcuminDisks Large Homolog 4 ProteinFemaleHeat-Shock ProteinsHippocampusHumansIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMiceMice, TransgenicAnti-Inflammatory Agents, Non-SteroidalCurcuminDisks Large Homolog 4 ProteinDLG4 protein, humanFYN protein, humanFyn protein, mouseHeat-Shock ProteinsIntracellular Signaling Peptides and ProteinsMAPT protein, humanMembrane ProteinsNR2B NMDA receptorProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-fynReceptors, N-Methyl-D-Aspartatetau Proteins

Identifiers

PMID23264626
PMCPMC3567657
OpenAlexW2021000498

What OpenQuestion holds

Textmetadata
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.