Navigation Links
Mechanism of Alzheimer's suggests combination therapy needed
Date:3/17/2009

Researchers at the University of Illinois at Chicago College of Medicine have discovered a mode of action for mysterious but diagnostic protein snarls found in the brains of Alzheimer's patients that suggests a one-two punch of therapy may be needed to combat the neurodegenerative disease.

Alzheimer's disease, which may affect as many as 5 million Americans and is among the most costly diseases to society in the United States and Europe, is characterized by two distinctive protein malformations: amyloid plaques and tau tangles. Amyloid plaques are sticky deposits made up of a short protein called amyloid beta, and tau tangles are made of short filaments of the tau protein.

So far no one has been able to explain how amyloid beta and the tau tangles wreak their damage on the nervous system.

"We have known for a long time that amyloid beta was bad," said Scott Brady, professor and head of anatomy and cell biology at the UIC College of Medicine. "What we haven't understood is why it's bad."

The findings, reported in a new study appearing in the Proceedings of the National Academy of Sciences Online Early Edition for March 16-20, suggest promising new targets for combination therapy.

In previous work, published earlier this year, the researchers suggested how tau tangles work together with amyloid beta to create a perfect storm that destroys neural function and memory.

"Cell death occurs at a very late stage of the disease," said Brady, principal investigator of the study. "Long before the cells die they lose function, and that function is critical for the symptoms that we see."

Brady and his colleagues found that when short assemblies of amyloid -- rather than the long-chain plaques -- get inside neurons, they interfere with the cells' transport system. This limits their ability to send vital proteins and vesicles to where they are needed within the cell and interferes with the synaptic connections to other nerve cells.

"We know from study of several hereditary adult-onset neurodegenerative diseases that damage to the transport system, over time, results in loss of synaptic activity, a gradual dying back of the neurons, and eventual neuron death -- exactly the pattern of Alzheimer's disease progression," Brady said.

"Neurons have an enormous logistical problem," Brady said. "Their critical role in making connections may require them to be very large. Some of them have to reach half the body's length -- for a tall person, a meter or more." Even just within the brain, he said, neurons are tremendously long compared to other cells.

The fast axonal transport system responsible for moving proteins and vesicles from the neuron's cell body where they are made, down the long, trunk-like projection of the axon, to the functional areas where they are needed and back again depends on motor proteins that attach to the cargo -- a vesicle or protein -- and carry it along a track made of microtubules.

In the new study, Brady and his colleagues showed that the short assemblies of amyloid activate a transport-regulatory enzyme called CK2 that causes the motor protein to drop its cargo. They were also able to show that inhibition of CK2 is sufficient to prevent the effects of amyloid on transport.

In the earlier work, the researchers showed that tau tangles halt transport to the neuron periphery through other regulatory enzymes by causing the motor protein to release the microtubule track.

The researchers found that the CK2 activated by amyloid also works as a primer for one of the enzymes activated by tau tangles, GSK3.

"Now we have the perfect storm," said Brady. "Both amyloid and tau tangles cause problems. But when you put them together, you exacerbate the problems, creating the cascade of events that cause Alzheimer's loss of neural connections.

"It makes sense of why both have to be present to have Alzheimer's," he said.

"It is also telling us that treating one is not going to be sufficient," he said. "We're going to have to think in terms of combination therapies that will allow us to address many targets at once. This may explain why attempts to manipulate one or the other haven't been successful in patients."


'/>"/>

Contact: Jeanne Galatzer-Levy
jgala@uic.edu
312-996-1583
University of Illinois at Chicago
Source:Eurekalert

Related medicine news :

1. Researchers uncover novel mechanism that balances the sizes of functional areas in the brain
2. UCSD study reveals the regulatory mechanism of key enzyme
3. Ancient mechanism for coping with stresses also gives cancer a boost
4. UCSD study reveals the regulatory mechanism of key enzyme
5. Researchers at IRB Barcelona discover one of the mechanisms that prevents the spread of colon cancer
6. Researchers chart the genetic mechanisms behind the genesis of fat cells
7. Research suggests mechanism for acne drugs link to depression
8. St. Jude finds mechanism for faulty protein disposal
9. St. Jude Finds Mechanism for Faulty Protein Disposal
10. Study suggests nicotine addiction might be controlled by influencing brain mechanisms
11. Quality control mechanism tags defective sperm cells inside the body
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Apple ... care services, staged a mock evacuation of the facility as part of a disaster ... Fire Department, Echo Hose EMS and Shelton City Emergency Manager, as well as the ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Global Healthcare Management’s ... Alexandria Park in Milford, NJ. This free event, sponsored by Global Healthcare Management’s ... The fun run is geared towards children of all ages; it is a ...
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the ... danger possible to save lost souls in the Philippines. “The Journey: From the Mountains ... a dedicated teacher of the Bible. She has taught all ages and currently teaches ...
(Date:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and ... plans to open a flagship location in Covington, LA at 401 N. U.S. Highway ... store next to Office Depot in the Holiday Square shopping center. Its location allows ...
(Date:10/12/2017)... ... 2017 , ... Asante, a nationally recognized health system in ... existing home health joint venture through an agreement, effective October 1, 2017, to ... home health company with Asante, delivering clinically integrated care, for the past eight ...
Breaking Medicine News(10 mins):
(Date:10/10/2017)... -- NDS received FDA 510(k) clearance in May 2017 for its highly ... designed for endoscopy environments. An innovative secondary monitor solution, ZeroWire ... support the improvement of patient outcomes, procedural efficiency, and the lowering ... ... ...
(Date:10/4/2017)... 4, 2017  South Korean-based healthcare product Development Company ... "cprCUBE" on Kickstarter. The device will educate the user ... with better efficiency compared to the dated and pricey ... on efficacy of the compression for a more informed ... goal to raise $5,000. ...
(Date:10/2/2017)... 2017  Eli Lilly and Company (NYSE: ... third quarter of 2017 on Tuesday, October 24, 2017. ... day with the investment community and media to further ... call will begin at 9 a.m. Eastern time. Investors, ... webcast of the conference call through a link that ...
Breaking Medicine Technology: