While there is no current cure for Alzheimer’s disease and other forms of dementia, the research community is one step closer to finding treatment. Bioengineers at the University of Washington have designed a peptide structure that can stop harmful changes of the body’s normal proteins from folding into structures, linked to widespread diseases such as Alzheimer’s. These synthetic molecules do this by targeting a toxic intermediate phase. This discovery could lead way to diagnose and even treatment of many diseases that are hard to pin down and rarely have a cure, such as Alzheimer’s disease.
“If you can truly catch and neutralize the toxic version of these proteins, then you hopefully never get any further damage in the body,” said senior author Valerie Daggett, a UW professor of bioengineering. “What’s critical with this and what has never been done before is that a single peptide sequence will work against the toxic versions of a number of different amyloid proteins and peptides, regardless of their amino acid sequence or the normal 3-D structures.”
Alzheimer’s disease is part of a group of illnesses known as amyloid diseases. These diseases are linked to the buildup of abnormally folded proteins called fibrils or plaques. This buildup tends to happen naturally as we age, and to a certain extent, our bodies don’t break down these proteins as quickly as they should. This can cause higher concentrations of abnormal proteins in some parts of the body. Each amyloid disease has a unique abnormally folded protein or peptide structure. However, these diseases are often misdiagnosed because their symptoms can be similar and pinpointing which protein is present usually isn’t done until after death. This has led to many dementias being broadly diagnosed as Alzheimer’s disease without definitive proof, and other diseases can go undiagnosed and untreated.
The researchers have developed a protein structure, called “alpha sheet,” that complements the toxic structure of the amyloid proteins. The alpha sheet effectively attacks the toxic middle state that the protein goes through as it transitions from normal to abnormal. They hope that their designed compounds could be used as diagnostics for amyloid diseases and as drugs to treat the diseases or at least slow progression.