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Related Experiment Video

Updated: Jul 14, 2026

Using Live-Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons
10:38

Using Live-Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons

Published on: December 22, 2023

Reducing PI4KIIIα Levels or Activity Limits Tau Seed Internalization and Assembly in Human Cortical Neurons.

Eleonora Clemente1, Ramakrishnan Sivasubramanian1, Susanne Kordes2

  • 1Center for Regenerative Therapies TU Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany.

Cells
|July 13, 2026
PubMed
Summary

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Phosphatidylinositol 4-kinase type IIIα (PI4KIIIα) inhibition reduces tau protein aggregation and spreading, key features of neurodegenerative diseases like Alzheimer's. This kinase is a potential therapeutic target for slowing tau-mediated neurodegeneration.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Tau protein aggregation and spreading are hallmarks of neurodegenerative conditions, including Alzheimer's disease and frontotemporal dementia.
  • Understanding the molecular mechanisms regulating tau propagation is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of phosphatidylinositol 4-kinase type IIIα (PI4KIIIα) in the regulation of tau propagation.
  • To identify PI4KIIIα as a potential therapeutic target for neurodegenerative diseases characterized by tau pathology.

Main Methods:

  • Utilized tau biosensor cells to assess the impact of PI4KIIIα inhibition and genetic reduction on tau aggregation seeding.
  • Generated induced pluripotent stem (iPS) cell-derived cortical neurons with pathogenic MAPT mutations for in vitro modeling of tau pathology.
Keywords:
PI4KAPI4KIIIαdisease modelingiPS cellsinduced pluripotent stem cellsprion-like spreadingtautauopathy

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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

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Last Updated: Jul 14, 2026

Using Live&#45;Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons
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Using Live-Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons

Published on: December 22, 2023

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
09:22

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

  • Developed phenotypic assays to monitor tau propagation and aggregation in human neurons and tested small molecule inhibitors.

    • Main Results:

    • Pharmacological inhibition and genetic reduction of PI4KIIIα significantly decreased the seeding of tau aggregation by extracellular seeds in biosensor cells.
    • PI4KIIIα inhibition consistently reduced tau assembly seeding in patient-derived human neurons, confirming its role in tau pathology.
    • The study established a novel in vitro model using iPS cell-derived neurons for studying tauopathy.

    Conclusions:

    • PI4KIIIα is identified as a key regulator of tau pathology, specifically in the seeding of tau aggregates.
    • Inhibition of PI4KIIIα presents a promising therapeutic strategy to slow or prevent tau-mediated neurodegeneration.
    • The developed experimental platforms offer new tools to study tau propagation mechanisms and discover novel therapeutic interventions.