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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
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Pioglitazone prevents tau oligomerization.
Tadanori Hamano1, Norimichi Shirafuji2, Chiemi Makino2
1Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan; Life Science Innovation Center, University of Fukui, Fukui, Japan.
Biochemical and Biophysical Research Communications
|August 21, 2016
Summary
Pioglitazone, a PPARγ agonist, effectively reduces tau aggregation in Alzheimer's disease models. This suggests PPARγ agonists could be valuable therapeutic agents for treating Alzheimer's disease.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Alzheimer's disease (AD) is characterized by tau aggregation and amyloid-beta (Aβ) deposition.
- Peroxisome proliferator-activated receptor gamma (PPARγ) activation influences Aβ production.
- The therapeutic potential of PPARγ agonists against tau pathology in AD remains to be fully elucidated.
Purpose of the Study:
- To investigate the efficacy of the PPARγ agonist pioglitazone (PIO) in preventing tau aggregation in Alzheimer's disease (AD).
Main Methods:
- Utilized a cellular model overexpressing wild-type tau protein (4R0N) and primary neuronal cultures.
- Assessed the effects of PIO on tau phosphorylation, total tau levels, and key signaling pathways (Akt, glycogen synthase kinase 3β, caspase3).
- Employed fractionation studies to analyze high molecular weight, oligomeric tau species.
Main Results:
- PIO significantly reduced both phosphorylated and total tau levels.
- PIO inactivated glycogen synthase kinase 3β, a key tau kinase, and activated Akt.
- PIO decreased caspase-mediated cleavage of tau, reducing aggregation-prone species and high molecular weight tau oligomers.
- The effects of PIO were reversed by the PPARγ antagonist GW9662.
Conclusions:
- PPARγ activation, as demonstrated by pioglitazone, effectively mitigates tau aggregation and related pathological markers in cellular models of Alzheimer's disease.
- These findings support the potential of PPARγ agonists as a therapeutic strategy for Alzheimer's disease, targeting tau pathology.
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