Cells that become "neurokillers" may be a new target for treating neurodegenerative diseases.

You may not have noticed astrocytes before, but they are quite a lot in your body.neuroscientists estimate that more than half of the cells in the brain are astrocytes.under normal circumstances, they provide important support for neurons.however, these cells may "go bad.".recently, a research team from the New York stem cell foundation (nyscf) published a research paper in neuron, a well-known academic journal of neuroscience, for the first time confirmed in human astrocytes that these friendly neuronal supporters can turn into the killers of toxic neurons in case of disease.researchers pointed out that the study of how astrocytes can produce toxicity to neurons can open up a new therapeutic approach for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis.the astrocytes that make stars in the brain get their name because they look like stars.according to Dr. Valentina fossati, who led the study, if neurons are compared to babies, astrocytes are like nannies."astrocytes feed neurons, clean neurons and keep them healthy."she explained.} the cultured astrocytes showed typical "astrocytes" (photo source: reference [2]; Credit: lilianne bar, the nyscf Research Institute). However, such "nanny" cells have not received much attention in research and drug development in the past.it was only in recent years that more and more evidence began to show that astrocytes are also associated with many nervous system diseases.however, most of the studies on astrocytes were carried out in mouse models, and mouse astrocytes are not exactly the same as human astrocytes.this means that many aspects of human astrocyte function, including some behaviors that may be related to disease, are not fully captured by mouse models."a reliable way to produce human astrocytes from stem cells is needed so that we can better study how they may cause neurodegenerative diseases," Dr. fossati said.Dr fossati's team has successfully transformed pluripotent stem cells into several other types of glial cells in the past, such as microglia (immune cells in the brain) and oligodendrocytes (cells that assist in neuronal communication).this time, they found a special protein cd49f expressed in astrocytes in order to produce astrocytes. using this protein as a "tag", researchers can identify astrocytes from the cultured mixed cell population for further research. "We are very excited to see that stem cell derived astrocytes derived from cd49f behave like typical astrocytes: ingesting glutamate and reacting to inflammation," Dr. fossati said, Phagocytosis, and promote the formation of mature firing patterns and connections of neurons. The team also confirmed the presence of cd49f in astrocytes found in human brain tissue. "we observed brain tissue samples from healthy donors and AD patients, and found that these astrocytes also express cd49f, suggesting that this protein is a reliable indicator of astrocyte identity in both healthy and diseased conditions. "deteriorated" astrocytes have produced functional astrocytes from stem cells, and the team has turned their attention to how these cells start "mood swings" in diseases. Dr. Shane liddelow of New York University (NYU) was a co-author of the study. his previous studies in mice have shown that astrocytes are toxic to the neurons they support. "we observed in mice that astrocytes in the inflammatory environment were reactive, actually attacking rather than supporting neurons. "he said," but we don't know if the cellular changes seen in rodents are the same in human cells. "} enjoy a group of stem cell derived astrocytes (photo source: reference [2]; Credit: lilianne bar, the nyscf Research Institute). Therefore, Dr. fossati's team exposed healthy stem cell derived astrocytes to inflammatory environment, basically simulating the brain environment of neurodegenerative diseases. this inflammatory exposure causes astrocytes to change shape, lose their "stellar light" and become more contractile. What's more, their work supporting neurons is getting worse. Dr fossati collected astrocyte byproducts and exposed these secretions to healthy neurons. "as you can see in mice, neurons in the culture dish begin to die," Dr. fossati said. "this phenomenon of" bad astrocytes "observed in human disease models suggests that it can also happen in real patients. this opens the door for new therapeutic drugs to intervene in the process. In addition to secreting a toxin that kills neurons, we also found that the astrocytes derived from stem cells can not work normally in the environment of similar diseases, which may lead to neuronal dysfunction. "Dr fossati explained," for example, they can't ingest glutamate correctly. Excessive glutamate is likely to stay around neurons, which may lead to neuronal atrophy, which is a potential target in new therapies. "conclusion the findings open up new research approaches and provide a new system for exploring the mechanism of disease. "I look forward to using our new system to further explore the intricate function of astrocytes in Alzheimer's disease, multiple sclerosis, Parkinson's disease and other diseases," Dr. fossati commented. "we have seen intriguing behaviors that may explain how neurodegenerative diseases occur. I hope this work will open the door to effective drug discovery and bring new therapies to patients. "reference [1] lilianne bar et al., (2020) cd49f is a new marker of functional and reactive human IPSC derived astrocytes. Neuron. Doi: nyscf scientists create the 'stars' of the brain and capture their rogue behavior in disease. Retrieved June 2, 2020, from When astrocytes attack: Stem cell model shows possible mechanism behind neurodegeneration. Retrieved June 2, 2020, from