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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
09:22

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

Pathogenesis of the tauopathies

Michel Goedert1, Maria Grazia Spillantini

  • 1MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK. mg@mrc-lmb.cam.ac.uk

Journal of Molecular Neuroscience : MN
|July 26, 2011
PubMed

Insights

Microtubule-associated protein tau (tau) misfolding causes neurodegenerative diseases like frontotemporal dementia. Evidence suggests multiple tau protein structures (conformers) contribute to disease diversity.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Microtubule-associated protein tau (tau) is implicated in neurodegenerative diseases.
  • Tau protein misfolding, hyperphosphorylation, and filament formation are hallmarks of tauopathies.
  • Mutations in the MAPT gene explain a subset of frontotemporal dementia cases, demonstrating tau's role in neurodegeneration.

Purpose of the Study:

  • To explore the role of tau protein dysfunction in neurodegenerative diseases.
  • To investigate the heterogeneity observed in tauopathies despite conserved hyperphosphorylation sites.
  • To provide experimental support for the concept of distinct tau conformers.

Main Methods:

  • Analysis of MAPT gene mutations in frontotemporal dementia.
  • Comparative analysis of hyperphosphorylated tau sites across different tauopathies.
  • Investigation of tau filament morphologies and isoform compositions.
  • Experimental validation of multiple tau conformers.

Main Results:

  • MAPT mutations are linked to frontotemporal dementia and parkinsonism.
  • Similar hyperphosphorylation sites exist across tauopathies, yet filament structures and tau isoforms differ.
  • Experimental data support the existence of multiple tau conformers.

Conclusions:

  • Tau protein dysfunction is sufficient to cause neurodegeneration and dementia.
  • The variability in tauopathies suggests the involvement of different tau conformers.
  • Understanding tau conformers is crucial for deciphering tauopathy pathogenesis.

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