At the Department of Energy researchers using powerful computers have generated a promising lead that may effectively treat patients with Parkinson’s. At least half a million people in the U.S. are believed to suffer from Parkinson’s with about 50,000 new cases diagnosed each year according to the National Institute of Neurological Disorders and Stroke.
A team of researchers at the Supercomputer Center at the University of California at San Diego used the Blue Gene/P supercomputer at the Department of Energy’s Argonne National Laboratory to simulate how proteins called alpha-synucleins damage neurons. Proteins are the cell’s workhorses carrying out vital maintenance and metabolic functions. Clumps of alpha-synucleins in the brain have long been associated with Parkinson’s and other degenerative diseases, but by the time clumps appear, the damage has already been done.
The simulation shows in much detail how alpha-synucleins actually join into ring-like structures penetrating cell membranes and creating pores long before clumps appear. In the case of Parkinson’s disease, the pores can lead to death in the brain’s dopamine-producing cells causing loss of mobility and other symptoms that worsen over time.
Researchers are also developing compounds that can stop alpha-synucleins aggregation in cell cultures. This is a first step toward developing a drug to treat and slow Parkinson’s progression. The information gained from this research is being applied to finding medical answers to Alzheimer’s disease, kidney diseases, and some cancers.
Research scientists at Argonne National Laboratory are also using their lab’s supercomputer to probe other secrets of the brain and find better treatments for patients with blood flow complications. In this study, researchers are mapping exactly how red blood cells move through the brain.
For example, healthy red blood cells are smooth and elastic since they need to squeeze and bend through tiny capillaries to deliver blood to all areas of the brain. By using the supercomputer, researchers were able to discover how the malaria parasite makes its victims red blood cells 50 times stiffer than normal. These malaria-infected cells stiffen and stick to the walls, creating blockages in arteries and vessels. Malaria victims die because their brain tissues are deprived of oxygen.
What is needed is a more complete picture of how blood moves through the brain so that doctors will be able to understand the progression of diseases that affect blood flow, like not only malaria but also diabetes, and HIV.
“Previous computer models haven’t been able to accurately account for the motion of blood cells bending or buckling as they ricochet off the walls,” said Joe Insley, a Principal Software Developer at Argonne who is working with the team. “So far the research data from the Argonne supercomputer is providing an extra level of detail to see how the brain actually works.”
Another part of the study is looking at the relationship between cerebrospinal fluid and blood flow in the brain. “Since blood vessels expand if blood pressure is high and since they are located between brain tissues, this can put dangerous pressure on the brain,” said Leopold Grinberg, a Brown University Scientist on the team.
In healthy people, spinal fluid can drain to relieve pressure on brain tissues, but occasionally the system breaks down—leaving the brain vulnerable to damage. Researchers are spending many hours trying to understand how the system interacts so that doctors will more accurately be able to treat and protect the brain.
