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Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
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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

Hyperphosphorylation-induced tau oligomers.

Khalid Iqbal1, Cheng-Xin Gong, Fei Liu

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

Frontiers in Neurology
|August 23, 2013
PubMed
Summary
This summary is machine-generated.

In Alzheimer disease, abnormal tau protein hyperphosphorylation drives the formation of toxic tau oligomers, disrupting microtubule networks and leading to neurofibrillary pathology in tauopathies.

Keywords:
Alzheimer diseaseAlzheimer neurofibrillary degenerationO-GlcNAcylation of tauabnormal hyperphosphorylation of taualternate splicing of taumicrotubule associated protein tauprotein phosphatase 2Atauopathies

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Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins
12:47

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins

Published on: December 27, 2016

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Normal tau protein is soluble and stabilizes microtubules.
  • In Alzheimer disease (AD), tau becomes hyperphosphorylated, altering its function.
  • This hyperphosphorylation is central to the development of tauopathies.

Purpose of the Study:

  • To investigate the role of tau hyperphosphorylation in the formation of tau oligomers.
  • To understand the mechanism of tau oligomerization and its impact on microtubule stability.
  • To explore the relationship between tau mutations, splicing dysregulation, and hyperphosphorylation in neurodegenerative diseases.

Main Methods:

  • Biochemical analysis of tau phosphorylation levels in normal and AD brains.
  • In vitro studies on tau dephosphorylation and rehyperphosphorylation using protein phosphatase 2A (PP2A) and tau protein kinases.
  • Investigation of tau self-assembly into paired helical filaments under physiological conditions.

Main Results:

  • Abnormally hyperphosphorylated tau (P-tau) forms soluble oligomers that sequester normal tau and other MAPs (MAP1, MAP2).
  • Tau oligomerization is dependent on hyperphosphorylation, as dephosphorylation inhibits and rehyperphosphorylation promotes it.
  • AD P-tau self-assembles into paired helical filaments, and tau mutations/splicing alterations contribute to hyperphosphorylation and pathology.

Conclusions:

  • Hyperphosphorylation is a critical driver of tau oligomerization and neurofibrillary pathology in AD and related tauopathies.
  • Aberrant tau phosphorylation disrupts microtubule networks, contributing to neuronal dysfunction.
  • Understanding tau hyperphosphorylation mechanisms is crucial for developing therapeutic strategies for tauopathies.