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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
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Aging dependent effect of nuclear tau.

Laura Gil1, Concetta Federico2, Fernando Pinedo3

  • 1Department of Genetics, Medical School, University "Alfonso X el Sabio", Madrid, Spain.

Brain Research
|October 5, 2017
PubMed
Summary

Phosphorylated nuclear tau (AT100) increases with cell aging and decreases in severe Alzheimer's disease (AD) and cancer. This finding suggests AT100 may serve as a molecular marker for cellular aging.

Keywords:
AT100AgingAging markerAlzheimer diseaseBreast acinar cellsCancerColorectal mucosaConfocal microscopyEpithelial cellsNeuronsNuclear tau

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Tau protein is found in the cytoplasm and nucleus, with complex phosphorylation patterns.
  • Nuclear tau phosphorylated at Thr212/Ser214 (AT100) has been observed to decrease in specific brain regions in Alzheimer's disease (AD).
  • The precise function of nuclear tau remains largely undefined.

Purpose of the Study:

  • To investigate the role and distribution of AT100 nuclear tau during aging and in age-related diseases.
  • To determine if AT100 can serve as a molecular marker for cellular aging.

Main Methods:

  • Immunohistochemical analysis of AT100 localization in neuronal and non-neuronal cells.
  • Assessment of AT100 levels in different stages of aging, AD, and cancer.
  • Co-localization studies with DAPI-positive heterochromatin and nucleoli.

Main Results:

  • AT100 levels progressively increase in cell nuclei during aging.
  • AT100 decreases in severe stages of Alzheimer's disease (AD) and in cancer cells.
  • AT100 is found in the nucleolus and co-localizes with heterochromatin, peaking in senescent cells and early AD (ADI), then disappearing in late AD (ADIV).

Conclusions:

  • Nuclear AT100 levels correlate with cellular aging.
  • The observed changes in AT100 during aging, neurodegeneration, and cancer suggest its potential as a molecular marker for cell aging.
  • Further research is warranted to elucidate the functional significance of nuclear AT100 in these cellular processes.