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Updated: Jun 25, 2026
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Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells
Published on: October 10, 2017
Omipalisib reduces hyperphosphorylated tau protein by modulating mTOR-autophagy pathway
Haeun Hwang1, Namkwon Kim2,3, Subyn Jeon1
1Department of Fundamental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
Plos One
|June 23, 2026
Summary
Omipalisib, a PI3K/mTOR inhibitor, activates autophagy to clear toxic tau protein aggregates. This treatment reduced tau levels and improved memory deficits in a mouse model of tauopathy.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Tauopathies are neurodegenerative diseases marked by abnormal tau protein accumulation.
- Autophagy, a cellular clearance process, is impaired in tauopathies, leading to protein buildup.
- Omipalisib is a dual PI3K/mTOR inhibitor investigated for its therapeutic potential.
Purpose of the Study:
- To investigate the efficacy of omipalisib in treating tauopathy in vitro and in vivo.
- To determine if omipalisib can activate autophagy and reduce tau pathology.
- To assess omipalisib's impact on cognitive function in a tauopathy model.
Main Methods:
- Utilized human tau-expressing SH-SY5Y cells (SH-Tau) to assess omipalisib's effects on autophagy markers (LC3B, p62) and tau phosphorylation.
- Administered omipalisib to PS19 mice, a model for tauopathy, and evaluated p-tau levels and spatial memory.
- Measured mTOR activation and cytotoxicity in treated cells.
Main Results:
- Omipalisib inhibited mTOR, increased LC3B, and decreased p62 in SH-Tau cells, indicating autophagy activation.
- Reduced tau phosphorylation and no observed cytotoxicity in SH-Tau cells.
- Omipalisib treatment in PS19 mice decreased soluble and insoluble p-tau levels and ameliorated spatial memory deficits.
Conclusions:
- Omipalisib effectively modulates the mTOR-autophagy pathway, reducing p-tau accumulation.
- Omipalisib demonstrates potential as a therapeutic agent for tauopathies by improving cognitive function.
- Targeting the PI3K/mTOR pathway with omipalisib offers a promising strategy for tauopathy treatment.
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