Navigation Links
Function found for Alzheimer's protein
Date:9/10/2010

In people with Alzheimer's, the brain becomes riddled with clumps of protein, forming what are known as amyloid plaques. Now, a report appearing in the September 17th print issue of Cell appears to have found a function for the amyloid precursor protein (APP for short) that yields the prime ingredient in those plaques.

It turns out that APP is an iron oxidase whose job it is to convert iron from an unsafe form to a safe one for transport or storage. When APP fails to function properly, as it does in Alzheimer's disease, iron levels inside neurons mount to toxic levels.

"This opens a big window on Alzheimer's disease and iron metabolism," said Ashley Bush of The Mental Health Research Institute, University of Melbourne.

"Although people have attributed several important physiological roles to APP," added Jack Rogers of Harvard Medical School, "this now gives us an idea of what this critical protein does to underpin its role in iron metabolism."

In fact, there were some clues. Some years ago, the researchers discovered that the RNA template for the APP protein includes an iron-responsive element. When iron levels rise, cells ramp up their APP production.

But amyloid in and of itself doesn't really explain what goes wrong in the Alzheimer's brain. "There has been a lot of attention on amyloid, but it seems it is not a simple matter of amyloid as the sole culprit," Bush said. For one thing, trials of drugs designed to target and clear amyloid plaques haven't worked as intended.

In fact, the disease is also complicated by high concentrations of metals, including iron that builds up inside neurons and zinc that accumulates within the amyloid plaques outside of those brain cells. And studies have also linked the loss of other iron oxidases to pathological iron accumulation and neurodegenerative diseases characterized by dementia. "If iron is left unbridled in its soluble form, it can cause nerve death and damage," Rogers said.

After 10 years of work, it appears Bush's and Roger's teams have connected the dots from the abnormal exchange of zinc to amyloid pathology and iron accumulation in Alzheimer's disease. "It's a sequence of dominoes falling onto each other," Bush said.

They show that APP is a bona fide iron oxidase, with properties much like the best-known iron oxidase (called ceruloplasmin), which is not expressed in neurons. Loss of APP in cells and primary neurons causes iron levels to build, while increasing APP promotes the export of iron out of cells.

Mice lacking APP become vulnerable to dietary iron, which causes the unsafe, oxidative form of iron to build in the animals' neurons, they show. Finally, they show that zinc in amyloid blocks APP's normal iron-balancing activities in the Alzheimer's brain.

Based on the new evidence, the researchers propose that elevated iron in the Alzheimer's brain summons further APP production. But that APP -- generated for the purpose of exporting iron -- gets disabled by high levels of zinc that dissociate from the amlyoid plaques.

The findings suggest that zinc may be an ideal target in the fight against Alzheimer's disease, the researchers say. In fact, studies in animals and early, short-term clinical trials of zinc-ionophore drugs including clioquinol and PBT2 in people with Alzheimer's disease have so far produced promising results. PBT2 is slated for further testing.

"Our findings authenticate zinc as a target," Bush said. "It really makes it look like an attractive place to hit."

Although Rogers said that he doesn't want to raise hopes for an Alzheimer's cure too high, "this is definitely an important step in getting to a therapy to retard the Alzheimer's disease process."


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. Home Care Delivered, Inc. Launches a New Vacuum Therapy Category to Service Patients with Erectile Dysfunction
2. Larynx preservation treatments result in low instance of severe voice disability, nutritional dysfunction
3. American Stroke Association Late-Breaking Science News Report: Stroke Survivors Can Improve Functioning of Paralyzed Arm Years After Stroke
4. Henry Ford Hospital study: Shoulder function not fully restored after surgery
5. New Liquid Functional Nutrition Products: EYL Beverages Announces Debut of DeCOMPRESS™ and Debug™ Beverages at Natural Products EXPO West
6. Erectile Dysfunction Plus Heart Disease Raises Death Risk
7. Smoking, but not past alcohol abuse, may impair mental function
8. Brain Function May Drop Quickly Before Alzheimers
9. Newly identified proteins critical to FA pathway DNA repair function
10. Jekyll and Hyde Factor May Control Insulin Function
11. Real Men Don't Take Erectile Dysfunction Drugs Without a Prescription
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/5/2016)... ... 05, 2016 , ... The event is being held on April 7, 2016 ... Minn. Triumph Over Parkinson’s will fund nearly $100,000 for research for the care and ... Parkinson’s disease and is the architect of this informative event to raise awareness and ...
(Date:2/5/2016)... ... February 05, 2016 , ... Looking for a last-minute ... at the tips of your toes. Foot massage, whether administered by a professional masseuse ... and relaxation. The American Board of Multiple Specialties in Podiatry (ABMSP) has ...
(Date:2/5/2016)... ... 2016 , ... The Lymphoma Research Foundation (LRF) – the ... the lymphoma community through a comprehensive series of education programs, outreach initiatives and ... Event at the La Gorce Country Club in Miami Beach on March 15, ...
(Date:2/5/2016)... Grants Pass, OR (PRWEB) , ... February 05, 2016 , ... ... though, with modern technology, such water may be safer than regular municipal or well ... water advocate and radio host Sharon Kleyne, could go a long way toward increasing ...
(Date:2/5/2016)... ... February 05, 2016 , ... Boar’s Head Brand®, one ... time for this weekend’s Big Game. Take the stress out of your party preparation ... your guests happy at every stage of the game. , “The key to hosting ...
Breaking Medicine News(10 mins):
(Date:2/4/2016)... 4, 2016  Edwards Lifesciences Corporation (NYSE: EW ... heart disease and critical care monitoring, announced today that ... agreement with Morgan Stanley & Co. LLC to repurchase ... part of the Company,s previously authorized program to repurchase ... --> --> ...
(Date:2/4/2016)... Wegener Polyangiitis - Pipeline Review, H2 ... Polyangiitis - Pipeline Review, H2 2015, provides an ... This report provides comprehensive information on the therapeutic ... at various stages, therapeutics assessment by drug target, ... and molecule type, along with latest updates, and ...
(Date:2/4/2016)... Feb. 4, 2016  Omnicell, Inc. (NASDAQ: OMCL ), ... to healthcare systems, today announced results for its fiscal ... --> --> GAAP results: Revenue ... up $5.1 million or 4.1% from the third quarter ... the fourth quarter of 2014. Revenue for the year ...
Breaking Medicine Technology: