Researchers have found that "natural killer" white blood cells could guard against the cascade of cellular changes that lead to Parkinson's disease and help stop its progression.

Natural killer (NK) cells are white blood cells that can kill tumors without being "told" from the body to do so. NK cells provide the first line of defense against invasion or a virus and are equipped with activating receptors that can sense cellular stress and identify cells that have been altered due to infection.

"Right now there's no available therapy to modify or stop the progression of Parkinson's," said lead author. "This would be the first NK study to show the possibility of actually stopping the disease."

Appearing in the current issue of Proceedings of the National Academy of Sciences, the new study highlights that NK cells act not only as efficient scavengers that attack an intruder but may be critical for regulating and restraining inflammation of brain tissue and protein clumping--hallmarks of Parkinson's and other neurodegenerative disorders. The report also found that NK cell depletion in a mouse model significantly exaggerated the disease condition. This led to the discovery that, without NK cells, the nervous system was left vulnerable to attack.

"We believe that NK cells exert protection by their ability to reduce inflammation in the brain and clear proteins that misfold and create toxic clumps," the author said. "In their absence, proteins were left unchecked, and we saw a substantial decrease in viral resistant cells, confirming that NK cells are a major source of signaling proteins that boost the immune system response."

The authors show that human NK cells can efficiently internalize and degrade α-syn aggregates via the endosomal/lysosomal pathway and decrease the release of the proinflammatory cytokine, IFN-γ. 

Thirty years ago, when research into immunotherapies got started, a logical first step in developing such therapies--to fight cancer, for example--was to train the immune system to recognize and attack tumor cells. Today, this idea has successfully moved from lab to clinic: New immunotherapies for melanoma, lung cancer and kidney cancer were recently approved by the U.S. Food and Drug Administration.

The author quick to caution that the Parkinson's work was done in animal models, but is optimistic about future immunotherapy discoveries and cited recent human trials that tested immunotherapies against an aggressive form of brain cancer called glioblastoma, indicating that NK cells contribute to elimination of tumor cells and release messages in support of defense of the immune system.

Parkinson's is no longer considered a brain-specific disease, and researchers increasingly recognize a functional connection between the immune system and central nervous system. The team found that, in conditions of chronic inflammation such as Parkinson's, the blood-brain barrier becomes disrupted, allowing immune cells to channel into the brain.

"Understanding how the periphery signals for NKs to patrol for infectious agents, even in the absence of disease, could lead to breakthrough treatments for Parkinson's disease," the author said.

Initially, the researchers have focused on the neuroprotective effects of NK cells. The next step is to study how NK cell functions are impaired by aging.

"Our preliminary data suggest that the number and function of NK cells are decreased in aged animals, and display impaired ability to perform their normal functions," the author said. "We would like to look deeper at age-related changes associated with NK cell biology and the wider implications for the health and well-being of older adults."

https://news.uga.edu/natural-killer-cells-halt-parkinsons-progression/

https://www.pnas.org/content/117/3/1762