Navigation Links
'Intrabody' can mop up mutant protein in Huntington's disease model
Date:5/25/2008

Scientists have created a tool for mopping up the clumps of mutant protein that drive neurodegeneration in Huntington's disease. Emory University researchers engineered a virus to make an intracellular antibody or "intrabody" against huntingtin, the protein whose mutant forms poison the brain cells of people with Huntington's.

Injecting the virus into the brains of mice that make mutant huntingtin improves their ability to move their limbs, although it does not prolong their lives.

The results will be published online and are scheduled for publication in the May/June issue of the Journal of Cell Biology.

Although other researchers have shown that various intrabodies can protect cells from mutant huntingtin, the Emory team was the first to examine the effects of an intrabody in living mice, says senior author Xiao-Jiang Li, PhD, professor of human genetics at Emory University School of Medicine.

Delivering the intrabody to brain tissues in people would be a formidable challenge, because it would require some form of gene therapy. However, it may be possible to use information about the intrabody's structure to find drugs that mimic its effects, Li says.

Huntington's affects about 30,000 people in the United States and usually begins in young- to mid-adulthood with the slow destruction of brain cells, leading to involuntary movements, cognitive impairment and sometimes depression or paranoia. Another 150,000 people are believed to have mutations that cause the disease, but have not begun to show clinical symptoms. The disease is fatal and currently there is no way to slow its development, although some medications can alleviate symptoms.

Disease-causing mutations involve a lengthening of part of the gene for huntingtin, so that it repeats three letters (CAG) of the genetic code dozens of times. Mutant proteins have a region consisting of the same amino acid (glutamine) many times, called poly-glutamine, which makes the proteins clump together inside brain cells.

Li says scientists who work on Huntington's have been studying where inside the cell the clumps have their toxic effect: brain cells' nuclei or in their axons and dendrites.

"Our goal here was to create a tool that could distinguish between the accumulation of mutant proteins in the nucleus and the cytoplasm," he says. "The intrabody binds huntingtin proteins with expanded poly-glutamine regions and it only works in the cytoplasm, not the nucleus."

Li and his colleagues showed that cultured cells that make both the intrabody and mutant huntingtin are able to get rid of the mutant protein faster and have fewer clumps of huntingtin.

Even though the intrabody only travels within the cytoplasm, it still alleviated the motor problems of mice that make mutant huntingtin when injected into the striatum, the scientists found. The striatum is the part of the brain most affected by Huntington's disease.

Li says finding an antibody that prefers to bind mutant, aggregated protein could also prove useful in the study of other neurodegenerative disorders, such as Alzheimer's disease or Creutzfeldt-Jakob disease.

"Several neurodegenerative diseases appear to involve defects in protein folding and metabolism, leading to the accumulation of protein aggregates inside cells," he says. "Our study suggests a strategy for dissecting the harmful effects of these protein aggregates in other diseases."

The clumps of mutant huntingtin are also seen in the neuronal nucleus and cytoplasm in a recently established transgenic monkey model of Huntington's, which was reported by Emory University researchers at http://whsc.emory.edu/press_releases2.cfm?announcement_id_seq=14304,


'/>"/>

Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert

Related medicine news :

1. What is the more suitable for early detection of low abundant lamivudine-resistant mutants?
2. FSU researchers mutant proteins could lead to new treatment for heart disease
3. Mutant gene causes epilepsy, intellectual disability in women
4. Effect of mutant p53 stability on tumorigenesis and drug design
5. Draining away brains toxic protein to stop Alzheimers
6. Penn study finds pro-death proteins required to regulate healthy immune function
7. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
8. Emory researchers identify signaling protein for multiple myeloma
9. Human C-reactive protein regulates myeloma tumor cell growth and survival
10. Lowering Blood Protein Wont Help Kidney Patients
11. Blood protein detects lung cancer, even at earliest stage
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... Many families have long-term insurance that covers ... companies have a waiver for care if the client has a cognitive impairment diagnosis. ... pays for care, is often waived, so the benefits from their insurance start immediately,” ...
(Date:10/13/2017)... ... October 13, 2017 , ... Talented host, ... lowdown on sciatica in a new episode of "Success Files," which is an ... and innovation and investigates each subject in-depth with passion and integrity. , Sciatica ...
(Date:10/12/2017)... ... October 12, 2017 , ... CitiDent and San Francisco ... using cutting-edge Oventus O2Vent technology. As many as 18 million Americans are estimated ... in breathing. Oral appliances can offer significant relief to about 75 percent of ...
(Date:10/12/2017)... ... ... Asante, a nationally recognized health system in southern Oregon, ... health joint venture through an agreement, effective October 1, 2017, to create AccentCare ... company with Asante, delivering clinically integrated care, for the past eight years. This ...
(Date:10/12/2017)... ... October 12, 2017 , ... On Saturday, October 21, the Health & ... by Moonlight to raise money for the American Heart Association Heart Walk. Teams of ... will work together to keep their treadmills moving for 5 hours. Treadmills will start ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... Oct. 12, 2017 West Pharmaceutical Services, ... solutions for injectable drug administration, today announced that it ... opens on Thursday, October 26, 2017, and will follow ... business expectations at 9:00 a.m. Eastern Time. To participate ... (International). The conference ID is 94093362. ...
(Date:10/11/2017)... Oct. 11, 2017  Caris Life Sciences ® , ... the promise of precision medicine, today announced that St. ... Precision Oncology Alliance™ (POA) as its 17 th ... St. Jude Crosson Cancer Institute will help develop standards ... of tumor profiling, making cancer treatment more precise and ...
(Date:10/11/2017)... , Oct. 11, 2017  Hill-Rom Holdings, Inc. ... Aspen Surgical facility in Las Piedras, Puerto ... scalpels and blades. ... that the facility sustained minor structural damage, temporary loss ... Maria. Repairs have been completed, manufacturing operations have resumed, ...
Breaking Medicine Technology: