A Lewy body, made largely of α-synuclein protein (blue), in a neuron. Lewy bodies are the pathologic hallmark of Parkinson’s disease.
The hallmark brain damage in Parkinson’s disease is thought to be the work of a misfolded, rogue protein that spreads from brain cell to brain cell like an infection. Now, researchers have found that the normal form of the protein—α-synuclein (αS)—may actually defend the intestines against invaders by marshaling key immune cells. But chronic intestinal infections could ultimately cause Parkinson’s, the scientists suggest, if αS migrates from overloaded nerves in the gut wall to the brain.
“The gut-brain immune axis seems to be on a cusp of an explosion of new insights, and this work offers an exceptionally exciting new hypothesis,” says Charles Bevins, an expert in intestinal immunity at the University of California, Davis, who was not involved with the study.
The normal function of αS has long been a mystery. Though the protein is known to accumulate in toxic clumps in the brain and the nerves of the gut wall in patients with Parkinson’s disease, no one was sure what it did in healthy people. Noting that a region of the αS molecule behaves similarly to small, microbe-targeting proteins that are part of the body’s immune defenses, Michael Zasloff, an immunologist at Georgetown University Medical Center in Washington, D.C., set out to find whether αS, too, might help fend off microbial invaders.