Proteins behaving badly
Several neurodegenerative diseases – including Alzheimer’s and ALS (Lou Gehrig’s disease) – are caused when the body’s own proteins fold incorrectly, recruit and convert healthy proteins to the misfolded form, and aggregate in large clumps that gum up the works of the nervous system. “For Star Trek fans, this is like the Borg, [a fictional race of cyborgs that abduct and assimilate humans and other species],” says Steven Plotkin, a biophysicist at the University of British Columbia in Vancouver who studies the process of protein misfolding.
Plotkin’s team has developed an algorithm that can predict which regions of a protein are prone to exposure upon misfolding, and how mutations in the protein and changes in the cellular environment might affect the stability of these vulnerable regions. These predictions help scientists gain a better understanding of protein dynamics, and may one day help in developing treatments to effectively combat currently incurable neurodegenerative diseases. The team will present its findings at the 56th Annual Meeting of the Biophysical Society (BPS), held Feb. 25-29 in San Diego, Calif.
The algorithm developed by Plotkin’s group uses the energy equations of thermodynamics to calculate the likelihood that certain stretches of protein will be displayed when the protein misfolds. Since the exposed regions are specific to the misfolded version of the protein, researchers can use these regions as targets for diagnostic and therapeutic treatments. The algorithm can be adapted for different proteins and predicts several potential target regions for each protein. The group has used it to study neurodegenerative disease-causing proteins as well as misfolded proteins that have been implicated in some cancers.
More recently, the research group used computer simulations to manipulate proteins in a virtual environment, testing out how easy it is for mutated proteins to misfold and propagate. Using this tool has helped the team predict the progression of hereditary ALS disease.
“The fact that we can predict the lifetime of an individual diagnosed with hereditary ALS from simulations of a protein’s mechanical properties is something that is both satisfying and that gives one pause,” says Plotkin. “We hope that such information might give some clues as to how to develop effective therapies for this disease.”
Definition of Lou Gehrig’s Disease
Lou Gehrig’s Disease, also called amyotrophic lateral sclerosis (ALS), a progressive and usually fatal disorder that attacks the nerves and muscles.
It is sometimes called Lou Gehrig’s disease, after the famed New York Yankee slugger whose death in 1941 was caused by this disorder.
The presentation, “Template-directed protein misfolding in silico and in the cell,” is at 1:45 p.m. on Tuesday, Feb. 28, 2012, in the San Diego Convention Center, Hall FGH.
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This news release was prepared for the Biophysical Society (BPS) by the American Institute of Physics (AIP).
Cause of Lou Gehrig’s Disease Discovered
Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s Disease is a severe rapidly progressive and fatal disease. It is a neurodegenerative disease in which motor nerves in the spinal cord die, causing the sufferer to become gradually paralyzed to the point of death over a brief 2 or 3 year time frame.
For years the cause of ALS has eluded scientists, until now.
A research group at Northwestern Medicine has just reported they have determined the cause of ALS and have published the results in the journal Nature.
The researchers determined the problem of ALS lies in the cellular pathway by which proteins in nerve cells are recycled.
Normally proteins are built to perform various cellular tasks including machinery to move components around the cell. As these proteins become damaged through wear and tear, they are recycled.
In ALS it now appears, the system used to perform that recycling is impaired. The defect appears to be in a newly discovered protein called ubiquilin2 that normally chaperones the defective proteins for recycling into proteosomes, a cellular recycling center. Instead, the defective proteins as well as ubiquilin2 accumulate within the cells. The collective material bogs down all cellular activity eventually causing them to die. These reams of protein skeins are observed in nerve cells from ALS patients.
ABOUT THE 2012 ANNUAL MEETING
Each year, the Biophysical Society Annual Meeting brings together over 6,000 research scientists in the multidisciplinary fields representing biophysics. With more than 4,000 poster presentations, over 200 exhibits, and more than 20 symposia, the BPS Annual Meeting is the largest meeting of biophysicists in the world. Despite its size, the meeting retains its small-meeting flavor through its subgroup meetings, platform sessions, social activities, and committee programs.
The 56th Annual Meeting will be held at the San Diego Convention Center (111 W. Harbor Drive, San Diego, CA 92101), located three miles from the San Diego International Airport and less than one mile from the Amtrak station. The San Diego Trolley has two stops directly in front of the Center at Harbor Drive/First Avenue and Harbor Drive/Fifth Avenue.
PRESS REGISTRATION
The Biophysical Society invites credentialed journalists, freelance reporters working on assignment, and public information officers to attend its Annual Meeting free of charge. For more information on registering as a member of the press, contact Ellen Weiss, Director of Public Affairs and Communications (.(JavaScript must be enabled to view this email address), 240-290-5606).
ABOUT BPS
The Biophysical Society (BPS), founded in 1956, is a professional scientific society established to encourage development and dissemination of knowledge in biophysics. The Society promotes growth in this expanding field through its annual meeting, monthly journal, and committee and outreach activities. Its 9000 members are located throughout the U.S. and the world, where they teach and conduct research in colleges, universities, laboratories, government agencies, and industry.
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Ellen R. Weiss
.(JavaScript must be enabled to view this email address)
240-290-5606
American Institute of Physics