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In the brain, the complement system plays a vital role in the normal development of the body and the immune response and synaptic elimination during the onset of disease; Inflammation in the brain and overactivation of the immune system can lead to synaptic loss and neuronal hope, which in turn can lead to neurodegenerative and psychiatric diseases
。 Recently, a study entitled "Small molecule screen reveals pathways that regulate C4 secretion in stem-cell derived astrocytes" published in the international journal Stem Cell Reports, scientists from Harvard University and other institutions said through research, Stem cells may help identify new drugs
for schizophrenia in humans.
In schizophrenia, the level of immune protein C4 in the brain, and the increase in C4 level due to copy number changes is directly related to the increased risk of schizophrenia, and therapies that can reduce the level of C4 protein and inflammation in the brain may benefit patients with schizophrenia, but they cannot be used
at present.
Brain cells called astrocytes regulate the body's immune response and inflammatory environment by secreting immune proteins such as C4, so astrocytes are a major target
of therapies to lower C4 levels.
Scientists use stem cells to create a large number of human astrocytes that secrete special immune proteins, which may hopefully help treat human schizophrenia
.
Image source: Stem Cell Reports (2022).
DOI:10.
1016/j.
stemcr.
2022.
11.
018
In this study, in order to identify effective drugs, the researchers developed an effective method to use stem cells to create a large number of human astrocytes that secrete the C4 protein
.
The researchers screened 464 drugs and identified a small group of about 20 drugs that could help reduce the secretion of C4 protein by astrocytes; These drugs are effective not only in healthy astrocytes, but also in astrocytes made from stem cells of people with schizophrenia
.
This study provides a new path for scientists to study the inflammatory response in human astrocytes and the regulatory mechanism behind it, and it can also be used as a special platform to help identify novel therapeutic drugs in large-scale screening.
In summary, the results of this study may lay a certain foundation
for later scientists to develop new therapies for central nervous system diseases involving complement cascade signaling.
(Biovalley Bioon.
com)
Original source:
Francesca Rapino,Ted Natoli,Francesco Limone,et al.
Small molecule screen reveals pathways that regulate C4 secretion in stem-cell derived astrocytes, Stem Cell Reports (2022).
DOI: 10.
1016/j.
stemcr.
2022.
11.
018