Researchers at Johns Hopkins have identified a protein that facilitates a toxic natural aggregate to spread from cell to cell in a mammal’s brain — and a method to block that protein’s action.  Ted Dawson, M.D., Ph.D., director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine reports that the new findings deal with the process by which aggregates of α-synuclein protein enter brain cells. Abnormal clumps of α-synuclein protein are often evident in autopsies of people with Parkinson’s disease and are believed to be the cause of destruction of dopamine-producing brain cells.

According to an article in Science Daily , current researchers are influenced by a theory published a few years ago which suggested that Parkinson’s disease progresses as α-synuclein aggregates spread from brain cell to brain cell, inducing previously normal α-synuclein protein to aggregate, and gradually move from the “lower” brain structures responsible for movement and basic functions to “higher” areas associated with processes like memory and reasoning.  Researchers, including Valina Dawson, Ph.D., professor of neurology, and Han Seok Ko, Ph.D., assistant professor of neurology, began to work together to examine how the aggregates enter cells.

The researchers began with studying transmembrane receptors, which are found on the outside of a cell and work like a lock in a door, admitting only proteins with the right “key.” They looked to see if any would allow the offending aggregates in. Three identified proteins did allow the aggregate through. One of the proteins, LAG3, showed a  distinct preference for latching on to α-synuclein aggregates over nonclumped α-synuclein.

The next step was to breed mice that lacked the gene for LAG3 and injected them with α-synuclein aggregates. “Typical mice develop Parkinson’s-like symptoms soon after they’re injected, and within six months, half of their dopamine-making neurons die,” Dawson says. “But mice without LAG3 were almost completely protected from these effects.” Antibodies that blocked LAG3 had similar protective effects in cultured neurons, the researchers found. (from ScienceDaily.com)

Xiaobo Mao, Ph.D, a research associate who works with Dawson, expressed excitement that they were able to identify both how the α-synuclein aggregates spread through the brain, but also how to stop their progress. Dawson notes that antibodies targeting LAG3 are currently in clinical trials to determine whether they can strengthen the immune system during chemotherapy. If those trials prove the drugs’ safety, the process of testing them as therapeutics for Parkinsons’ disease might be sped up, he says.