Activation of PKR Causes Amyloid ß-Peptide Accumulation via De-Repression of BACE1 Expression
2011

How Herpes Virus Affects Alzheimer's Disease

publication 10 minutes Evidence: moderate

Author Information

Author(s): ILL-Raga Gerard, Palomer Ernest, Wozniak Matthew A., Ramos-Fernández Eva, Bosch-Morató Mònica, Tajes Marta, Guix Francesc X., Galán José J., Clarimón Jordi, Antúnez Carmen, Real Luis M., Boada Mercé, Itzhaki Ruth F., Fandos César, Muñoz Francisco J.

Primary Institution: Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain

Hypothesis

Does the activation of PKR by herpes simplex virus type 1 (HSV1) lead to increased BACE1 expression and amyloid beta accumulation in Alzheimer's disease?

Conclusion

The study suggests that HSV1 activates PKR, which in turn increases BACE1 translation and amyloid beta production, potentially contributing to Alzheimer's disease.

Supporting Evidence

  • HSV1 infection activates PKR in neuroblastoma cells.
  • Activated PKR leads to increased BACE1 expression.
  • Poly (I∶C) treatment mimics viral infection and increases Aß production.
  • PKR activation is linked to Alzheimer's disease pathology.
  • BACE1 translation is regulated by eIF2-alpha phosphorylation.
  • HSV1 DNA is found in Alzheimer's disease brain tissue.
  • PKR activation co-localizes with BACE1 expression in AD brains.

Takeaway

This study found that a virus can make a protein in the brain that is linked to Alzheimer's disease work more, which might make the disease worse.

Methodology

The study used neuroblastoma cells and mouse tissue to investigate the effects of HSV1 on PKR activation and BACE1 expression.

Limitations

The study primarily focuses on in vitro and animal models, which may not fully replicate human Alzheimer's disease.

Statistical Information

P-Value

p<0.0005

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0021456

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