Science of Parkinsons Monthly Research Review: January 2022 is out

scienceofparkinsons.com/202...

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Thanks for sharing. This was interesting:

Puzzling Parkinson’s protein plays essential role in immunity science.org/content/article...

"Progress in treating Parkinson’s disease—a progressive neurological illness that causes tremors, muscle rigidity, and dementia—has been painfully slow, in large part because scientists still don’t fully understand the molecular events that kill select brain cells. What they do know is Parkinson’s leaves behind a telltale mark: clumps of the misfolded alpha synuclein (αS) protein in the brains and guts of patients at autopsy. In its normal form, the protein is widely thought to help brain cells communicate, but researchers have now uncovered another role—αS plays an essential part in immune and inflammatory responses in the gut.

The new work is “extremely well done and very exciting,” says physician-scientist Michael Schlossmacher, who studies Parkinson’s disease at the Ottawa Hospital Research Institute but was not involved with the study. He adds that the protein’s “pivotal role” in immunity may help explain why chronic infection or inflammation can lead to a higher risk of Parkinson’s.

Others in the field, however, question the work’s relevance to the brain disorder. The dominant view among researchers is that misfolded αS aggregates and takes on new toxic properties, and some say the natural role of the protein, although interesting, may be irrelevant to pursuing needed treatments.

Parkinson’s disease, the second most common neurodegenerative ailment after Alzheimer’s, affects one in 331, or about 1 million, people in the United States and at least 7 million people globally. Many patients are diagnosed in their 60s, as brain cells that make the neurotransmitter dopamine die and lead to symptoms. But the disease can also strike the young—including those who produce too much αS, or fail to break it down—because of rare genetic mutations. Other risk factors include sex—prevalence is 40% to 50% higher in men than in women—and some chronic inflammatory diseases, such as inflammatory bowel disease and chronic hepatitis C. Oral dopamine can mitigate symptoms, but the 60-year-old treatment isn’t a cure and ultimately fails to prevent worsening symptoms and death.

But some scientists are increasingly convinced that αS’s normal functions may play a role in causing the disease, and need to be clearly defined to make progress. Abundant inside brain cells, αS is thought to be central to the functioning of synapses, the communication junctions between neurons. But its exact role at these sites has largely remained a mystery. “We are terrible at treating Parkinson’s,” says David Beckham a neurovirologist at the University of Colorado School of Medicine. “Because we just have no clue what this protein is doing.”

Recent work has started to suggest another role—in immunity. In 2016, Beckham and colleagues discovered neurons in people and mice whose brains were infected by West Nile virus made αS in response. In mice genetically engineered to lack αS, the severity of the brain infection and the mortality of the disease were far worse. And a 2017 study found that, in children with gastrointestinal inflammation and intestinal transplant recipients infected with norovirus, nerve endings in the inflamed walls of the upper intestine secreted αS. The more inflammation, the more αS was made. Crucially, that study demonstrated that the released αS attracted inflammatory cells and stimulated the maturation of dendritic cells, key defenders that present bits of foreign pathogens to white blood cells, kicking off an immune response."