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

Bibliographic

Year of Publication:
2013
Contact PI Name:
Sally A. Frautschy
Contact PI Affiliation:
Veterans Greater Los Angeles Healthcare System, Geriatric Research Education and Clinical Center, Los Angeles, California, USA
Co-Authors:
Qiu-Lan Ma, 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
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Alzheimer's Association
United States Department of Veterans Affairs (VA)
Siegel Life Foundation
National Institute of Neurological Disorders and Stroke (NINDS)
Study Goal and Principal Findings:

This study aimed at investigating the effects of curcumin on tau pathology and neuron loss in late stage, tangle bearing hTau mouse model of tauopathy. Curcumin treatment was found to selectively suppress levels of soluble tau dimers, but not insoluble and monomeric phospho-Tau, In addition curcumin corrected behavioral, synaptic, and  deficits in heat shock protein (HSP) expression.  Curcumin treatment elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response.  Curcumin treatment  differentially impacted HSP90 client kinases, reducing Fyn kinase without reducing Akt kinase. In summary, intervention with curcumin at late stage in tangle-bearing mice reduced soluble Tau oligomers and Fyn kinase, perhaps through increasing HSP70, HSP90, and HSC70, which have the potential to clear misfolded Tau.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
Curcumin
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
Tau
Strain/Genetic Background:
C57Bl/6J

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Y Maze
Novel Object Recognition Test (NORT)
Morris Water Maze
Biochemical
Tau Dimers
Postsynaptic Density Protein 95 (PSD95)
Heat Shock Proteins
Tyrosine Protein Kinase FYN
Protein Kinase B (Akt/PKB)
Tau Oligomers
Immunochemistry
Glutamate Ionotropic Receptor NMDA Type Subunit 2B (GluN2B/NR2B)
Pharmacokinetics
Drug Concentration-Brain
Drug Concentration-Plasma