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:2/24/2017)... ... February 24, 2017 , ... Healthcare Associates of McKinney announced today ... building at 8080 State Highway 121, Suite 210, McKinney, Texas 75070. It is ... 121. , As the practice has grown, the need for more space has been ...
(Date:2/24/2017)... ... February 24, 2017 , ... The California State ... convening academic faculty engaged in or interested in palliative care education and research. The ... be held in North County San Diego on Sept. 28 and 29, 2017, on ...
(Date:2/24/2017)... ... ... Fiber Network (IFN) President and CEO Kelly C. Dyer recently announced that he will ... the Management Committee when IFN was originally formed in 2002 where he was ultimately ... of the business plan. He became the first paid employee of IFN in ...
(Date:2/24/2017)... (PRWEB) , ... February 24, 2017 , ... ... qualifying into the Senior International Elite division on February 12th. Ms. Esparza ... divisions at the elite qualifier competition held in Las Vegas, Nevada. Frida is ...
(Date:2/23/2017)... ... February 23, 2017 , ... On February 22, 2017 the ... to withdraw previous guidance issued by the Obama Administration requiring schools to ... May 2016 by the Obama Administration came in response to a growing number ...
Breaking Medicine News(10 mins):
(Date:2/24/2017)... Following receiving CE Marking in Europe ... AMAR is a major milestone for the country where the device was developed ... market in Israel   ... inclusion in the National Health Basket , Israel , ... E-QURE Corp. (OTCQB: EQUR), a leader in medical devices for the treatment of advanced wound ...
(Date:2/24/2017)... -- Research and Markets has announced the addition of the ... 2025" report to their offering. ... The Global Empty Capsules Market is poised to grow at ... $2.9 billion by 2025. This industry report analyzes the ... well as regional levels presented in the research scope. The study provides ...
(Date:2/24/2017)... Physician General Dr. Rachel Levine ... Jennifer Smith commended South Central EMS today for ... naloxone, a life-saving overdose reversal drug. The recognition event ... and overdose survivor who was saved due to the ... significant part of fighting the opioid epidemic is making ...
Breaking Medicine Technology: