Proteins — tools of living cells — can’t do their job if they’re not in shape. Literally.
And a new study is the first to image the various stages of a protein’s undoing, which will lend valuable insight to treatment of diseases such as Alzheimer’s and Parkinson’s.
Those are just two of the diseases caused by proteins that are misfolded — their amino acid chains are not arranged correctly, resulting in a misshapen three-dimensional structure. When misfolded, these proteins don’t work and, in the case of diseases such as Alzheimer’s, gunk up the brain and eventually destroy nerve cells.
Understanding how proteins fold is crucial to developing ways to prevent and treat these diseases. Previous attempts to document the process have involved heat or chemicals, creating conditions under which the proteins quickly unraveled and thus limiting observation of the in-between states.
Artist’s rendering of a mitochondrian, the energy-producing
cellular structure affected by ARSACS
Scientists have pinpointed the cause of a rare, fatal neurodegenerative disorder called ARSACS, or autosomal recessive spastic ataxia of Charlevoix-Saguenay. The disease is due to defects in neuron’s mitochondria, the bit of biological machinery that generates energy for the cell—a structure known to be affected in Parkinson’s, Alzheimer’s, and other neurological diseases, as well.
ARSACS was first observed in the descendants of a small group of 17th century French settlers who made their homes near the Charlevoix and Saguenay rivers in what is now Quebec, and has since been seen worldwide. But its incidence remains unusually high in that particular French Canadian community, with 1 in 1,500 to 2,000 people developing ARSACS and 1 in 23 people unaffected genetic carriers of the disease.
Neurons damaged by Parkinson’s disease
What’s the News: Scientists have reversed Parkinson’s disease-like brain damage and motor problems in mice and rats using neurons grown from human embryonic stem cells. The new technique, described online in Nature earlier this week, brings scientists closer to similar treatments for people with Parkinson’s.
What’s the News: When personal genotyping service 23andMe was founded in 2006, most people were understandably focused on the benefits and the dangers of knowing your chances of getting an incurable disease. But a major part of the company’s business plan was eventually leveraging their users’ information to explore the genetic basis of disease.
With more than 100,000 people now in their database, 23andMe has been turning that into a reality. They’ve just published their first paper focusing on the origins of disease, pinpointing two new areas of the genome involved in Parkinson’s.
What’s the News: The bacterium that causes ulcers and some stomach cancers, Helicobacter pylori, could at least contribute to Parkinson’s disease, according to a new study in mice presented at a microbiology conference yesterday. Mice infected with H. pylori have shown Parkinson’s-like symptoms, building on earlier work that has suggested a link between the bacteria and Parkonson’s disease.
Back in the 1980s, gene therapy was one of science’s greatest hopes and hypes, and researchers predicted the technique would be used to cure a huge range of illnesses. During the 90s, many early gene therapy trials were effective or downright dangerous, some causing cancer or even death. But more recently, scientists who stuck with gene therapy have started to see positive results, with promising treatments for malformed hemoglobin, color blindness, and depression. (See the DISCOVER magazine feature “The Second Coming of Gene Therapy” for more.) Now, researchers have announced that they’ve successfully treated the symptoms of Parkinson’s disease in a small group of people—a far cry from a cure, but still a step in the right direction.
I Once Was Blind but Now I See
The theory behind gene therapy is simple: A healthy gene hitches a ride into the patient’s genome on a virus, replacing the genes responsible for some genetic disease or disorder. Actually doing this is more difficult, because humans have a little thing called an immune system that’s remarkably efficient at finding and destroying foreign bodies. After the first U.S. death from gene therapy in 1999, and leukemia cases in France the same year, many started to think that gene therapy was more of a problem than an answer.
The early and awful failures forced all of the researchers in the field to retreat and reconsider the staggering complexity that challenged them. They could not just replace a bad gene with a good gene, as some early pundits had hoped—they also had to orchestrate the nuanced and elaborate dance between the gene products (proteins) and the patient’s immune system, which could recognize a foreign body and viciously attack it. After that was settled, gene therapists still had to find a suitable virus, or vector, to carry replacement genes into human cells without inciting a damaging or deadly immune response…. It was this new perspective more than anything else that turned gene therapy from a simple but failed and frustrated hope into, once again, medicine’s next big thing—a stunning spectacle of hubris, ignominy, and redemption on the scientific stage. [DISCOVER]
New: Gene Therapy and Parkinson’s Disease
While there’s no cure for Parkinson’s as of yet, doctors have an arsenal of methods, ranging from drugs, brain stimulation, and (now) gene therapy that help reduce the disease’s symptoms. Hopes for using gene therapy to alleviate Parkinson’s effects aren’t new. What is new is that scientists have successfully completed the first randomized, controlled, double-blind trial of treating Parkison’s patients with gene therapy—and they found that it significantly improved debilitating symptoms such as tremors, motor skill problems, and rigidity. Read More
Picture the classic shoot-out in a Western movie: The good guy and the bad guy face each other, their hands quivering over their gun holsters. The bad guy reaches for his weapon, causing the good guy to react–he whips out his pistol and BAM! The hero triumphs. Physicist Niels Bohr once had a theory on why the good guy always won shoot-outs in Hollywood westerns. It was simple: the bad guy always drew first. That left the good guy to react unthinkingly – and therefore faster. When Bohr tested his hypothesis with toy pistols and colleagues who drew first, he always won [New Scientist].
But new research suggests that Bohr didn’t have it exactly right. In a study published in Proceedings of the Royal Society B, scientists suggest that people do move faster when they are reacting to what is happening around them–but not fast enough for a heroic gunslinger to save his own life.
It wasn’t quite as dramatic as a slow-motion movie action sequence or a slo-mo instant reply, but researchers have successfully slowed down people’s manipulation of a computer joystick by boosting one type of brain wave. The researchers generated a small electrical current in the brains of 14 healthy volunteers using scalp electrodes. The current increased the activity of normal beta waves [New Scientist], and slowed the volunteers’ reaction times by 10 percent. The study, published in Current Biology, has implications for Parkinson’s Disease, in which patients have trouble with voluntary motions.
Brain waves are generated naturally when groups of neurons fire in a certain rhythm. Lead researcher Peter Brown explains that the low-frequency beta waves were already known to play a role in movement. “Different parts of the brain work together and generate certain frequencies,” he explained, “and the movement areas of the brain come together in beta activity. That activity is suppressed just prior to and during movement, so we think the body gets rid of it to prepare to make a new movement” [BBC News].
Inserting a “pacemaker” into the brain to emit regular pulses of electricity and quell disordered neural activity may sound like a therapy of last resort, but if current experiments show beneficial results the brain surgery may one day be commonplace. But some scientists are cautioning that research on so-called deep brain stimulation may be pressing ahead too quickly, and warn that long-term effects of the surgery are not yet clear.
A growing number of psychiatric researchers are testing the method’s effectiveness on a host of psychiatric disorders. Until recently, deep brain stimulation was approved in the U.S. only to treat certain movement disorders, primarily those of Parkinson’s disease, for which it diminishes tremors and rigidity and improves mobility. To date, more than 60,000 patients worldwide have had the devices implanted [Los Angeles Times]. But now large clinical trials are in the works that will test the use of deep brain stimulation for obsessive compulsive disorder, epilepsy, and depression. Smaller experiments are beginning to assess the therapy’s effectiveness on a wide range of disorders including anorexia, drug addiction, obesity, traumatic brain injury, and Alzheimer’s.