Related Experiment Video

Updated: Jun 22, 2025

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
09:22

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

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G-protein coupled receptors regulates Tauopathy in neurodegeneration

Subashchandrabose Chinnathambi1, Hariharakrishnan Chidambaram1

  • 1Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences (NIMHANS), Institute of National Importance, Bangalore, Karnataka, India.

Advances in Protein Chemistry and Structural Biology
|July 3, 2024
PubMed

Insights

Microglia

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Alzheimer's disease involves Tau protein misfolding and aggregation.
  • Microglia, brain macrophages, respond to extracellular Tau deposits.
  • Purinergic receptors mediate microglial migration to inflammation sites.

Purpose of the Study:

  • To investigate the interaction between the Tau repeat-domain (TauRD) and the microglial P2Y12 receptor.
  • To elucidate the role of P2Y12 receptor in Tau internalization and microglial activation.

Main Methods:

  • In-silico analysis to identify interaction residues between TauRD and P2Y12 receptor.
  • Cellular studies including co-immunoprecipitation and western blot to confirm interaction and expression.
  • Analysis of microglial activation markers (Iba1) and TauRD localization.

Main Results:

  • TauRD interacts with the microglial P2Y12 receptor.
  • This interaction induces P2Y12 receptor expression and TauRD internalization.
  • P2Y12 receptor-mediated internalization activates microglia and leads to TauRD accumulation for degradation.

Conclusions:

  • The microglial P2Y12 receptor plays a crucial role in Tau internalization and microglial response.
  • Targeting the P2Y12 receptor could be a therapeutic strategy for Alzheimer's disease by modulating microglial phagocytosis of Tau.

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