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Related Experiment Videos

c-Jun phosphorylation in Alzheimer disease.

Akanksha Thakur1, Xinglong Wang, Sandra L Siedlak

  • 1Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.

Journal of Neuroscience Research
|April 25, 2007
PubMed
Summary
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Alzheimer disease (AD) brains show altered c-Jun phosphorylation, particularly phospho-c-Jun (Ser73), linked to neurofibrillary tangles and GVD, suggesting a protective adaptation rather than apoptosis.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pathology

Background:

  • The c-Jun N-terminal kinase (JNK) pathway is activated by oxidative stress and implicated in Alzheimer disease (AD).
  • c-Jun, a downstream target of JNK, requires phosphorylation at Ser63/Ser73 for activation.

Purpose of the Study:

  • To compare the localization of phospho-c-Jun (Ser63) and phospho-c-Jun (Ser73) in the hippocampi of AD cases versus controls.
  • To investigate the relationship between c-Jun phosphorylation, neurofibrillary tangles, granulovacuolar degeneration (GVD), and neuronal apoptosis in AD.

Main Methods:

  • Immunohistochemical analysis of phospho-c-Jun (Ser63) and phospho-c-Jun (Ser73) in hippocampal tissues from AD patients and age-matched controls.
  • Assessment of co-localization with neurofibrillary tangles and GVD.

Related Experiment Videos

  • TUNEL assay to evaluate apoptosis.

    • Main Results:

    • Phospho-c-Jun (Ser73) strongly associated with neurofibrillary tangles and GVD in AD neurons; phospho-c-Jun (Ser63) associated with GVD.
    • Phospho-c-Jun (Ser73) staining was more extensive than phospho-c-Jun (Ser63), with complete overlap.
    • Neurons with cytoplasmic phospho-c-Jun (Ser73) in GVD were TUNEL-negative, suggesting a non-apoptotic role.

    Conclusions:

    • Specific alterations in c-Jun phosphorylation and distribution occur in AD hippocampi.
    • These alterations, particularly phospho-c-Jun (Ser73) in GVD, may represent a cellular adaptation to oxidative stress rather than a direct trigger for apoptosis.