Navigation Links
Protein can nurture or devastate brain cells, depending on its 'friends,' researchers find
Date:11/11/2008

DALLAS Nov. 11, 2008 Researchers at UT Southwestern Medical Center have uncovered new insights into the "Dr. Jekyll and Mr. Hyde" nature of a protein that stimulates stem-cell maturation in the brain but, paradoxically, can also lead to nerve-cell damage.

In two separate studies in mice scheduled to appear online this week and in an upcoming issue of the Proceedings of the National Academy of Sciences, UT Southwestern research teams studied the protein Cdk5 and discovered both helpful and detrimental mechanisms it elicits in nerve cells.

Dr. Amelia Eisch, assistant professor of psychiatry at UT Southwestern, and her colleagues uncovered a beneficial mechanism of the helpful "Dr. Jekyll" side of the Cdk5 protein, which is also thought to kill brain cells and contribute to neurodegenerative diseases such as Alzheimer's. In the current study, Dr. Eisch found that Cdk5, together with its activating partner molecule p35, helps immature nerve cells become fully functional.

In a separate study, Dr. James Bibb, associate professor of psychiatry at UT Southwestern, found yet another harmful action of the Cdk5 protein. It can stunt learning and reduce motor control.

Cdk5 is a kinase, which means its job is to interact with all sorts of other proteins inside cells and modify them through a process called protein phosphorylation. Whether Cdk5 nurtures or devastates depends on the state of its partner and the proteins it modifies.

"Like all of us, Cdk5 can influence others, in this case other proteins," Dr. Eisch said. "When Cdk5 messes with hooligans, it causes big trouble. When it hangs with the straight-A students, it actually helps other cells reach their full potential."

Dr. Eisch studied different stages of neurogenesis, or the formation of new nerve cells, in the brains of adult mice and found that the absence of Cdk5 prevents neural stem cells from maturing. She and her group used advanced genetic engineering to create mice in which they could turn off Cdk5 within nerve cells in a specific region of the brain where new neurons are born.

Dr. Eisch found that when Cdk5 is removed from immature nerve stem cells, normal cell division occurs, but the nerve cells never reach maturity. Researchers also removed Cdk5 from neighboring mature nerve cells and discovered that this removal resulted in the production of fewer immature nerve cells.

"The techniques we used have moved us several steps beyond what is usually done in the field," Dr. Eisch said. "We're beginning to assemble a dictionary of what regulates neurogenesis. By understanding what's vital at each stage of development, we hopefully can one day manipulate human nerve cells so that the brain can withstand neurodegenerative diseases such as Alzheimer's."

Dr. Bibb studied the "Mr. Hyde" component of Cdk5. Using a different but equally advanced set of genetic approaches, his team studied the effects of turning Cdk5 to the "dark side" by expressing a shortened form of the Cdk5 activating partner called p25. The group found that when paired with p25 in deep brain structures, Cdk5 had destructive effects on motor coordination and learning in the mice.

Neuropsychiatric illnesses such as schizophrenia, attention deficit hyperactivity disorder and drug addiction involve similar brain pathways as the ones studied and implicated in the "Mr. Hyde" aspect of Cdk5, Dr. Bibb said.

Dr. Bibb also used new technology to reach deeper inside the brain and explore regions beyond those typically examined in conjunction with neurodegenerative diseases. His team used a green fluorescent protein to trace Cdk5's activity in mice, allowing the researchers to examine precisely what was happening in the brain when the Cdk5/p25 pairing was overexpressed.

They found that the overexpression damaged circuitry in the area of the brain that controls movement and reward-based learning. The brain cells lost about half of their connections, or synapses, with other brain cells. This was accompanied by inflammation usually associated with neurodegeneration.

"Once we saw the loss of synapses, we understood why the mice experienced problems with movement and learning," Dr. Bibb said. "Surprisingly, despite the negative effects of putting Cdk5 with p25 in this part of the brain, the cells didn't die. Researchers now have the tools to delve deeper into the brain to study disease. Being unable to control movement, or having psychiatric illness, can be as devastating as memory loss."

Dr. Eisch will next study why immature cells need Cdk5/p35 and why the loss of Cdk5 in neighboring mature nerve cells stopped development.

Dr. Bibb's work will focus on blocking Cdk5 from causing negative reactions and trying to determine how Cdk5/p25 is created.


'/>"/>

Contact: LaKisha Ladson
lakisha.ladson@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

Related medicine news :

1. Statin Reduces Heart Attack, Stroke Rates in Patients With Normal Cholesterol but Elevated C-Reactive Protein
2. Omega Protein Reports 17 Cents Per Share Third Quarter Profit
3. Signaling between protein, growth factor is critical for coordinated cell migration
4. Quintet of proteins forms new, early-warning blood test before heart attack strikes
5. Cell Biosciences Introduces First Protein Analysis Kits
6. The Wellness(R) Core(R) Family Continues to Grow With New Higher Protein, Grain-Free Canned Varieties for Cats and Dogs
7. Key Blood Test Protein May Not Cause Heart Disease
8. Elaborate Network Drives When and Where Proteins Are Made
9. NIAID awards contracts to search for protein markers of disease
10. MBL scientist Osamu Shimomura wins Nobel Prize for discovery of green fluorescent protein
11. New way to control protein activity could lead to cancer therapies
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Protein can nurture or devastate brain cells, depending on its 'friends,' researchers find
(Date:5/26/2016)... Miami, FL (PRWEB) , ... May 26, 2016 , ... ... day of events featuring guest speaker Dr. Adonis Maiquez MD, ABAARM. Dr. Adonis ... Anti-Aging and Regenerative Medicine, and a member of the Institute for Functional Medicine. , ...
(Date:5/26/2016)... ... May 26, 2016 , ... Bunion Bootie , the ... bunionette) treatment was more than humbled by customer demand over the Mother’s Day Weekend ... mid sale. Now that Bunion Bootie has completely replenished its inventory levels, it hopes ...
(Date:5/26/2016)... Redwood City, CA (PRWEB) , ... May 26, 2016 , ... ... time, Silicon Valley-based startup, The Dough Bar, has ignited an undeniable buzz ... shake -- a doughnut. But not just any doughnut.  These doughnuts are packed with ...
(Date:5/26/2016)... ... May 26, 2016 , ... Metcalf & Associates’ ... 20 years of experience in leading technology and human resources operations for health ... teaching, Morrow-Fox will be featured on Metcalf’s VoiceAmerica radio show , Innovative ...
(Date:5/26/2016)... ... , ... Dr. LeRoy Perry’s recently authored whitepaper, “Tech Neck and ROI (return ... of users, hundreds of millions of whom are coming into the workplace with pain ... common action of looking down at hand-held technology devices (tablets, smartphones) for extended periods ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... -- FDA 510(k) clearance covers Confocal ... urological and surgical applications Mauna Kea ... the multidisciplinary confocal laser endomicroscopy (CLE) platform, today ... with the 12 th 510(k) clearance from ... new FDA clearance covers Confocal Miniprobes indicated for ...
(Date:5/25/2016)... Germany and GERMANTOWN, Maryland , ... QGEN ; Frankfurt Prime Standard: QIA) today announced ... agreement with Therawis Diagnostics GmbH to develop and commercialize predictive ... and market PITX2 as a marker to predict effectiveness of ... patients. "We are pleased to partner with Therawis, ...
(Date:5/25/2016)... 25, 2016 According to market ... Growth and Demand Forecast to 2022 - Industry Insights ... Others)" published by P&S Market Research, the global insulin ... 2015, and it is expected to grow at a ... insulin pump segment is expected to witness the fastest ...
Breaking Medicine Technology: