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Groundbreaking Protein Structure Developed To Interfere With Formation Of Amyloid Plague

 

'Alpha sheet' developed by the University of Washington: Diagram:University of Washington'Alpha sheet' developed by the University of Washington: Diagram:University of WashingtonAlzheimer's, Parkinson's, rheumatoid arthritis, Type 2 diabetes, atherosclerosis...  These are just five of the more than 40 identified amyloid diseases, serious diseases that currently have limited treatments and no cure.  But, after 10 years of research, bioengineers at the University of Washington (UW) have created a novel protein that can stop the amyloid protein in its tracks....

Amyloids are proteins in the body that accumulate naturally as we age.. What amyloids generally do is stick to each other and to healthy proteins in our bodies, forming plaques or fibrils.  The accumulation of this plaque is what causes many serious diseases.  You've probably heard of the beta-amyloid  plaque that can accumulate in the brain and cause Alzheimer's disease.

A UW former graduate student, Roger Armen, discovered through computer models, a secondary structure capable of attacking a protein as it goes from a normal state to an amyloid state.  Finally, 10 years later, the lab has succeeded in actually building and testing this structure, it calls the alpha sheet, or alpha-amyloid.  In the model below, you can see how this mechanism works.

 

How the "alpha sheet" works: University of WashingtonHow the "alpha sheet" works: University of Washington

 

In the diagram above,  the researchers demonstrate 1) how the normal protein becomes an amyloid protein and forms a fibril (upper portion of diagram) and 2) how an alpha-sheet can intervene by attaching itself to the normal protein before it becomes an amyloid protein (lower portion of diagram).

Right now this design is more than hypothetical.  Though human testing has not been done, UW laboratory experiments have been successful.  The amazing thing is that the alpha-sheet has been effective in all the disease samples tested, so an Alzheimers amyloid protein could be successfully interrupted with the same alpha-sheet as, say, a diabetes amyloid protein, even though the nature of the amyloids might not be exactly the same. In the future, however, some modifications to the alpha-sheet might prove to have even greater capabilities.

You can read the full study online in eLife. The researchers have applied for patents on the alpha-sheet and they are looking forward to their invention being used for early diagnoses and treatments for a host of amyloid diseases.  So are we.

 

sources: University of Washington via RDmag, eLife