New York : A team of researchers has identified a protein that enables a toxic natural aggregate to spread from cell to cell in the brain and reduce chances of Parkinson’s disease.
Abnormal clumps of a-synuclein protein are often found in autopsies of people with Parkinson’s disease and are thought to cause the death of dopamine producing brain cells.
In the study published in the journal Science, researchers said the new findings hinge on how aggregates of a-synuclein protein enter brain cells.
Previous research stated that Parkinson’s disease progresses as a-synuclein aggregates spread from brain cell to brain cell, inducing previously normal a-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.
“There was a lot of scepticism, but then other labs showed a-synuclein might spread from cell to cell,” said Valina Dawson, Professor at the Johns Hopkins University School of Medicine, US.
The researchers knew they were looking for a certain kind of protein called a transmembrane receptor, which is found on the outside of a cell and works like a lock in a door, admitting those cells were the only proteins with the right “key”.
They first found cells called a-synuclein aggregates which could not enter a line of human brain cancer cells grown in the laboratory. The next step was to add genes for transmembrane receptors one by one to the cells and see whether any of them allowed the aggregates in.
Three of the proteins did, and one, LAG3, had a heavy preference for latching on to a-synuclein aggregates over nonclumped a-synuclein.
The team next bred mice that lacked the gene for LAG3 and injected them with a-synuclein aggregates.
“Typical mice develop Parkinson’s-like symptoms soon after they were injected, and within six months, half of their dopamine-making neurons die. But mice without LAG3 were almost completely protected from these effects,” the study suggested.
The researchers suggested that an immunotherapy already in clinical trials as a cancer therapy should also be tested as a way to slow the progress of Parkinson’s disease.
Antibodies that blocked LAG3 had similar protective effects in cultured neurons, the researchers found.
Dawson noted that antibodies targeting LAG3 are already in clinical trials to test whether they can beef up the immune system during chemotherapy.