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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

Post-translational modifications of tau protein in Alzheimer's disease

C-X Gong1, F Liu, I Grundke-Iqbal

  • 1Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. cxgong@ultinet.net

Journal of Neural Transmission (Vienna, Austria : 1996)
|November 2, 2004
PubMed

Insights

Abnormal tau protein modifications, including hyperphosphorylation and glycosylation, drive Alzheimer's disease (AD) neurodegeneration. Targeting these tau changes offers potential therapies for AD and other tauopathies.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Microtubule-associated protein tau (MAPT) undergoes various post-translational modifications.
  • Aberrant tau modification and aggregation into paired helical filaments (PHFs) characterize Alzheimer's disease (AD) and tauopathies.
  • Key modifications include hyperphosphorylation and glycosylation, crucial for neurofibrillary degeneration.

Purpose of the Study:

  • To review abnormal post-translational modifications of tau.
  • To discuss the pathophysiological relevance of tau hyperphosphorylation and glycosylation in AD.
  • To examine cerebrospinal fluid biomarkers for total tau and phosphorylated tau.

Main Methods:

  • Literature review of tau post-translational modifications.
  • Analysis of pathophysiological roles of specific tau modifications.
  • Review of diagnostic biomarker studies for total tau and phosphorylated tau in cerebrospinal fluid.

Main Results:

  • Multiple tau modifications (e.g., ubiquitination, glycation) may indicate failed cellular clearance mechanisms.
  • Hyperphosphorylation and glycosylation are central to the molecular pathogenesis of AD.
  • Elevated total tau and phosphorylated tau in cerebrospinal fluid are significant diagnostic biomarkers.

Conclusions:

  • Understanding tau modifications is key to neurodegenerative disease pathogenesis.
  • Targeting abnormal tau modifications presents promising therapeutic strategies for AD and tauopathies.
  • Further research into tau modification pathways may reveal novel treatment avenues.

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