Navigation Links
New protein structure could help treat Alzheimer's, related diseases
Date:7/28/2014

There is no cure for Alzheimer's disease and other forms of dementia, but the research community is one step closer to finding treatment.

University of Washington bioengineers have a designed a peptide structure that can stop the harmful changes of the body's normal proteins into a state that's linked to widespread diseases such as Alzheimer's, Parkinson's, heart disease, Type 2 diabetes and Lou Gehrig's disease. The synthetic molecule blocks these proteins as they shift from their normal state into an abnormally folded form by targeting a toxic intermediate phase.

The discovery of a protein blocker could lead to ways to diagnose and even treat a large swath of diseases that are hard to pin down and rarely have a cure.

"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."

The findings were published online this month in the journal eLife.

More than 40 illnesses known as amyloid diseases Alzheimer's, Parkinson's and rheumatoid arthritis are a few are linked to the buildup of proteins after they have transformed from their normally folded, biologically active forms to abnormally folded, grouped deposits called fibrils or plaques. This happens naturally as we age, to a certain extent our bodies don't break down proteins as quickly as they should, causing higher concentrations in some parts of the body.

Each amyloid disease has a unique, abnormally folded protein or peptide structure, but often such diseases are misdiagnosed because symptoms can be similar and pinpointing which protein is present usually isn't done until after death, in an autopsy.

As a result, many dementias are broadly diagnosed as Alzheimer's disease without definitive proof, and other diseases can go undiagnosed and untreated.

The molecular structure of an amyloid protein can be only slightly different from a normal protein and can transform to a toxic state fairly easily, which is why amyloid diseases are so prevalent. The researchers built a protein structure, called "alpha sheet," that complements the toxic structure of amyloid proteins that they discovered in computer simulations. The alpha sheet effectively attacks the toxic middle state the protein goes through as it transitions from normal to abnormal.

The structures could be tailored even further to bind specifically with the proteins in certain diseases, which could be useful for specific therapies. The researchers hope their designed compounds could be used as diagnostics for amyloid diseases and as drugs to treat the diseases or at least slow progression.

"For example, patients could have a broad first-pass test done to see if they have an amyloid disease and then drill down further to determine which proteins are present to identify the specific disease," Daggett said.

The research team includes Gene Hopping, Jackson Kellock and James Bryers of UW bioengineering; Gabriele Varani and Ravi Pratap Barnwal of UW chemistry; Peter Law, a former UW graduate student; and Byron Caughey of the National Institutes of Health's Rocky Mountain Laboratories. Working with the UW's Center for Commercialization, they have a patent on one compound and have submitted an application to patent the entire class of related compounds.

This research began a decade ago in Daggett's lab when a former graduate student, Roger Armen, first discovered this new secondary structure through computer simulations. Daggett's team was able to prove its validity in recent years by designing stable compounds and testing their ability to bind toxic versions of different amyloid proteins in the lab.


'/>"/>

Contact: Michelle Ma
mcma@uw.edu
206-543-2580
University of Washington
Source:Eurekalert  

Related biology news :

1. A protein couple controls flow of information into the brains memory center
2. Protein evolution follows a modular principle
3. High matrix metalloproteinase-9 expression induces microangiogenesis after cerebral infarction
4. Scientists map one of most important proteins in life -- and cancer
5. Measuring the number of protein molecules inside cells
6. National Xenopus resource at the MBL innovates new way to study proteins
7. Cell membrane proteins give up their secrets
8. Proteins hands enable bacteria to establish infection, research finds
9. SLU scientists hit delete: Removing regions of shape-shifting protein explains how blood clots
10. CNIO scientists develop technology to redirect proteins towards specific areas of the genome
11. Research reveals how key controller protein is switched on
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New protein structure could help treat Alzheimer's, related diseases
(Date:6/20/2016)... , June 20, 2016 Securus ... justice technology solutions for public safety, investigation, corrections ... the prisons involved, it has secured the final ... (DOC) facilities for Managed Access Systems (MAS) installed. ... additional facilities to be installed by October, 2016. ...
(Date:6/15/2016)... , June 15, 2016 ... report titled "Gesture Recognition Market by Application Market - Global Industry ... - 2024". According to the report, the  global gesture ... in 2015 and is estimated to grow at ... billion by 2024.  Increasing application of ...
(Date:6/9/2016)... TURKU, Finland , June 9, 2016 ... French National Police deploy Teleste,s video security solution to ensure ... France during the major tournament ... and data communications systems and services, announced today that its ... Police Prefecture to back up public safety across ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... LOUISVILLE, Ky. , June 23, 2016 /PRNewswire/ ... from two Phase 1 clinical trials of its ... double-blind, placebo-controlled, single and multiple ascending dose studies ... and pharmacodynamics (PD) of subcutaneous injection in healthy ... APL-2 subcutaneously (SC) either as a single dose ...
(Date:6/23/2016)... LONDON , June 23, 2016 ... & Hematology Review, 2016;12(1):22-8 http://doi.org/10.17925/OHR.2016.12.01.22 ... Review , the peer-reviewed journal from touchONCOLOGY, ... the escalating cost of cancer care is placing ... a result of expensive biologic therapies. With the ...
(Date:6/23/2016)... ... 23, 2016 , ... ClinCapture, the only free validated electronic ... showcase its product’s latest features from June 26 to June 30, 2016 for ... Disrupting Clinical Trials in The Cloud during the conference. DIA (Drug Information ...
(Date:6/23/2016)... ... June 23, 2016 , ... Velocity Products, a division ... tuned and optimized exclusively for Okuma CNC machining centers at The International Manufacturing ... collaboration among several companies with expertise in toolholding, cutting tools, machining dynamics and ...
Breaking Biology Technology: