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Tau protein spreads like an infection from cell to cell
Tom(ek)
Posted: Friday, February 3, 2012 11:52 AM
Joined: 12/21/2011
Posts: 62


Mouses:

 

"Alzheimer’s disease seems to spread like an infection from brain cell to brain cell, two new studies in mice have found. But instead of viruses or bacteria, what is being spread is a distorted protein known as tau."

 

http://www.nytimes.com/2012/02/02/health/research/alzheimers-spreads-like-a-virus-in-the-brain-studies-find.html

 

Now scientists understand how tau (and disease) can spread from neuron to neuron.


Lane Simonian
Posted: Friday, February 3, 2012 8:04 PM
Joined: 12/12/2011
Posts: 5089


Welcome back Tom(ek) and thank you for sharing this important research story. 

 

It may not be the spread of tau itself that is the problem, but the increased hyperphosphorylation of tau proteins.  Peroxynitrites may contribute to the hyperphosphorylation of tau proteins.

http://www.ncbi.nlm.nih.gov/pubmed/16816118 

Through oxidation, peroxynitrites may also contribute to the misfolding of the superoxide dismutase which then spreads to other parts of the brain (the superoxide dismutase converts the superoxide anion to hydrogen peroxide)..

http://onlinelibrary.wiley.com/doi/10.1002/ana.21319/abstract?systemMessage=Wiley+Online+Library+will+be+disrupted+4+Feb+from+10-12+GMT+for+monthly+maintenance 

http://www.ncbi.nlm.nih.gov/pubmed/21321227 

The spread of a defective superoxide dismutase to other parts of the brain would in turn increase peroxynitrite levels (as more superoxide anions would be able to combine with inducible nitric oxide to form peroxynitrites).  This may result in the hyperphosphorylation of tau proteins in some other parts of the brain.  What a vicious circle.

 

Peroxynitrites may also contribute to the misfolding of prions which in normal form appears to increase superoxide dismutate activity.   http://www.ncbi.nlm.nih.gov/pubmed/14713301 Moreover, the entombment of copper and zinc in amyloid plaques also dampens superoxide dismutase activity (the enzyme requires copper and zinc to function).  This is just one more piece of evidence that Alzheimer's disease is largely a disease caused by oxidative stress and that the best means to treat the disease are with selective antioxidants.

http://www.sciencedirect.com/science/article/pii/S0969996100902900 

http://lpi.oregonstate.edu/ss06/neurodegeneration.html