Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Uncover Biochemical Pathway by Which Harmful Molecule May Raise Alzheimer’s Risk

16.06.2010
A molecule implicated in Alzheimer’s disease interferes with brain cells by making them unable to “recycle” the surface receptors that respond to incoming signals, researchers at UT Southwestern Medical Center have found.

The harmful molecule, called APOE4, is present in about one out of every six people, the researchers said. Those with the gene for APOE4 have up to 10 times the risk of developing Alzheimer’s disease earlier in life than average.

The researchers discovered that APOE4 makes a nerve cell hold back the molecules that enables it to respond to other cells, thereby disabling a chemical process known to be important in learning. Their findings appear online this week in the Proceedings of the National Academy of Sciences.

“This is actually a fairly simple system,” said Dr. Joachim Herz, director of the Center for Alzheimer’s and Neurodegenerative Disease at UT Southwestern and senior author of the study. “For the first time, we see an uninterrupted biochemical pathway that links the surface of the brain cell to the dysfunction inside the cell, and specifically at the junction at which nerve cells communicate.”

The research focused on a basic characteristic of nerve cells called neurotransmission, in which they use chemicals to signal each other. When one nerve cell needs to “talk” to another, its tip sends out a chemical called a neurotransmitter. The surface of the second cell is studded with molecules called receptors, which fit specific neurotransmitters like a lock and key. When a neurotransmitter docks onto its receptor, the second cell responds.

A cell can fine-tune its sensitivity by removing receptors from its surface. To do this, the cell engulfs the receptors to its interior, taking them out of action. It can eventually recycle them back to the surface, where they can respond to neurotransmitters again.

The researchers looked at receptors that respond to a neurotransmitter called glutamate, which is implicated in memory and learning. In mice that were genetically altered to make human APOE4, the researchers found that APOE4 prevented the cells from accomplishing a vital step in learning – becoming more sensitive to repeated signals.

The researchers also studied the mice’s hippocampus – an area of the brain vital to learning – to see how it would respond to extracts from the brain of a human with Alzheimer’s. The extract prevented both normal and genetically altered mice from processing incoming signals; however, the normal mice could recover from this suppression, while the mice with APOE4 could not.

Dr. Herz and his colleagues hypothesized that APOE4 exerted its effects by interacting with the receptors for a molecule called Reelin, which keeps brain cells more sensitive to each other. Both APOE4 and Reelin bind to the same receptor. When Reelin binds to it, the combination triggers a biochemical cascade that makes the glutamate receptor more sensitive to incoming signals.

The researchers showed that APOE4 prevents the Reelin-binding receptor from being recycled back to the surface. With fewer receptors, the nerve cell can’t bind much Reelin, no matter how much is around. Without Reelin’s effects, the cell doesn’t respond as vigorously to glutamate, and doesn’t “learn” as well.

Knowing how a biological system works doesn’t automatically translate to clinical use, Dr. Herz cautioned. “Although these findings constitute a milestone in our understanding of how APOE4 becomes such a potent risk factor for Alzheimer’s disease, potential drugs that might come from this finding would still require years of development,” he said.

“The question is, now that we’ve apparently identified what’s going on, can we do anything about this disease process at the fundamental molecular level? That’s what we’re working on right now,” Dr. Herz said.

Other UT Southwestern researchers involved in the study were graduate student Ying Chen; Dr. Murat Durakoglugil, assistant instructor of molecular genetics; and Dr. Xunde Xian, postdoctoral researcher in molecular genetics.

The study was funded by the National Institutes of Health, the American Health Assistance Foundation, the Perot Family Foundation, the Consortium for Frontotemporal Dementia Research, SFB780 and the Humboldt Foundation.

Visit http://www.utsouthwestern.org/neurosciences to learn more about UT Southwestern’s clinical services in the neurosciences, including treatment of all types of neurovascular and neuromuscular disorders.

Aline McKenzie | Newswise Science News
Further information:
http://www.utsouthwestern.org/neurosciences

More articles from Life Sciences:

nachricht Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie

nachricht Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Molecular Force Sensors

20.09.2017 | Life Sciences

Producing electricity during flight

20.09.2017 | Power and Electrical Engineering

Tiny lasers from a gallery of whispers

20.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>