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Written | Edited by Wang Cong | Typesetting by Wang Duoyu | Shui Chengwen The most important organ of our human beings, the brain, contains tens of billions of interacting neurons.
They are very important and very fragile, and need to be protected in a special environment.
to function normally
.
The blood-brain barrier (BBB) is an important protective mechanism.
A barrier that allows only certain types of molecules from the bloodstream to enter neurons and other surrounding cells in the brain
.
The existence of the blood-brain barrier is of great significance to prevent harmful substances from entering the brain from the blood.
However, the blood-brain barrier also prevents the transfer of most small molecules and macromolecules (such as polypeptides, proteins and nucleic acids), which severely limits the central Treatment of neurological disorders such as neurodegenerative diseases, brain tumors, brain infections and strokes,
etc.
Therefore, when a person suffers from a disease of the central nervous system, the blood-brain barrier, which originally played a protective role, becomes the "worst enemy"
.
Scientists have long wanted to find a way to temporarily open the blood-brain barrier for drug delivery and then reseal it
.
Recently, researchers from Yale University in the United States published a research paper entitled: Endothelial Unc5B controls blood-brain barrier integrity in the journal Nature Communications
.
This study revealed for the first time the molecular mechanism of regulating the blood-brain barrier.
The receptor Unc5B of vascular endothelial cells maintains the integrity of the blood-brain barrier by regulating the Wnt signaling pathway
.
Inhibiting the binding of Unc5B to its ligand Netrin-1 by an antibody can briefly open the blood-brain barrier and re-seal it within hours
.
This discovery opens new doors for future drug delivery and therapy targeting the central nervous system
.
The development and maintenance of the blood-brain barrier relies on the so-called Wnt signaling pathway, which regulates many key cellular processes, and the research team has been trying to figure out whether this signaling pathway can be modulated to open the blood-brain barrier "on demand
.
"
In 2017, Kevin Boyé (first author of the paper) joined the laboratory of Anne Eichmann (corresponding author of the paper) as a postdoc, and he began to study the Unc5B protein, an endothelial membrane receptor expressed in capillary endothelial cells protein
.
They found that if the Unc5B gene was knocked out in mice, they died early in embryonic development, due to the failure of the vasculature to form properly, suggesting that Unc5B is an important molecule in blood vessel development
.
They also found that a protein called Claudin5, which is important for establishing the blood-brain barrier between endothelial cells, was also significantly reduced
.
These findings led the research team to realize that Unc5B plays an important role in maintaining the blood-brain barrier
.
Previously, scientists did not know the link between Unc5B and the Wnt signaling pathway, but in this new study, they found that Unc5B actually controls the Wnt signaling pathway and acts as an upstream regulator
.
Next, the research team knocked out the Unc5B receptor in adult mice that had established a blood-brain barrier, and found that the mice's blood-brain barrier would open
.
They further found the ligand of Unc5B receptor, Netrin-1, and inhibiting this ligand can also open the blood-brain barrier
.
On this basis, the research team developed an antibody that inhibits the binding of Netrin-1 to Unc5B.
After intravenous injection of the antibody, the Wnt signaling pathway was disrupted, resulting in the temporary opening of the blood-brain barrier.
.
Collectively, this study demonstrates that the vascular endothelial cell receptor Unc5B maintains the integrity of the blood-brain barrier by regulating the Wnt signaling pathway
.
Mechanistically, Unc5B's ligand Netrin-1 enhanced the interaction of Unc5B with the Wnt co-receptor LRP6, induced its phosphorylation and activated Wnt/β-catenin downstream signaling
.
Intravenous delivery of antibodies that block Netrin-1 binding to Unc5B resulted in a transient disruption of Wnt signaling and opening of the blood-brain barrier, which resealed a few hours later
.
The existence of the blood-brain barrier prevents most small molecules and macromolecules from entering the brain.
Therefore, central nervous system diseases such as Alzheimer's disease, multiple sclerosis, brain tumors, and depression are extremely difficult to treat
.
This study uncovered for the first time the molecular mechanism that regulates the blood-brain barrier, so that the blood-brain barrier can be temporarily opened in a targeted manner, opening a new door for future drug delivery and treatment targeting the central nervous system
.
Paper link: https:// Open for reprinting, welcome to forward to Moments and WeChat groups
They are very important and very fragile, and need to be protected in a special environment.
to function normally
.
The blood-brain barrier (BBB) is an important protective mechanism.
A barrier that allows only certain types of molecules from the bloodstream to enter neurons and other surrounding cells in the brain
.
The existence of the blood-brain barrier is of great significance to prevent harmful substances from entering the brain from the blood.
However, the blood-brain barrier also prevents the transfer of most small molecules and macromolecules (such as polypeptides, proteins and nucleic acids), which severely limits the central Treatment of neurological disorders such as neurodegenerative diseases, brain tumors, brain infections and strokes,
etc.
Therefore, when a person suffers from a disease of the central nervous system, the blood-brain barrier, which originally played a protective role, becomes the "worst enemy"
.
Scientists have long wanted to find a way to temporarily open the blood-brain barrier for drug delivery and then reseal it
.
Recently, researchers from Yale University in the United States published a research paper entitled: Endothelial Unc5B controls blood-brain barrier integrity in the journal Nature Communications
.
This study revealed for the first time the molecular mechanism of regulating the blood-brain barrier.
The receptor Unc5B of vascular endothelial cells maintains the integrity of the blood-brain barrier by regulating the Wnt signaling pathway
.
Inhibiting the binding of Unc5B to its ligand Netrin-1 by an antibody can briefly open the blood-brain barrier and re-seal it within hours
.
This discovery opens new doors for future drug delivery and therapy targeting the central nervous system
.
The development and maintenance of the blood-brain barrier relies on the so-called Wnt signaling pathway, which regulates many key cellular processes, and the research team has been trying to figure out whether this signaling pathway can be modulated to open the blood-brain barrier "on demand
.
"
In 2017, Kevin Boyé (first author of the paper) joined the laboratory of Anne Eichmann (corresponding author of the paper) as a postdoc, and he began to study the Unc5B protein, an endothelial membrane receptor expressed in capillary endothelial cells protein
.
They found that if the Unc5B gene was knocked out in mice, they died early in embryonic development, due to the failure of the vasculature to form properly, suggesting that Unc5B is an important molecule in blood vessel development
.
They also found that a protein called Claudin5, which is important for establishing the blood-brain barrier between endothelial cells, was also significantly reduced
.
These findings led the research team to realize that Unc5B plays an important role in maintaining the blood-brain barrier
.
Previously, scientists did not know the link between Unc5B and the Wnt signaling pathway, but in this new study, they found that Unc5B actually controls the Wnt signaling pathway and acts as an upstream regulator
.
Next, the research team knocked out the Unc5B receptor in adult mice that had established a blood-brain barrier, and found that the mice's blood-brain barrier would open
.
They further found the ligand of Unc5B receptor, Netrin-1, and inhibiting this ligand can also open the blood-brain barrier
.
On this basis, the research team developed an antibody that inhibits the binding of Netrin-1 to Unc5B.
After intravenous injection of the antibody, the Wnt signaling pathway was disrupted, resulting in the temporary opening of the blood-brain barrier.
.
Collectively, this study demonstrates that the vascular endothelial cell receptor Unc5B maintains the integrity of the blood-brain barrier by regulating the Wnt signaling pathway
.
Mechanistically, Unc5B's ligand Netrin-1 enhanced the interaction of Unc5B with the Wnt co-receptor LRP6, induced its phosphorylation and activated Wnt/β-catenin downstream signaling
.
Intravenous delivery of antibodies that block Netrin-1 binding to Unc5B resulted in a transient disruption of Wnt signaling and opening of the blood-brain barrier, which resealed a few hours later
.
The existence of the blood-brain barrier prevents most small molecules and macromolecules from entering the brain.
Therefore, central nervous system diseases such as Alzheimer's disease, multiple sclerosis, brain tumors, and depression are extremely difficult to treat
.
This study uncovered for the first time the molecular mechanism that regulates the blood-brain barrier, so that the blood-brain barrier can be temporarily opened in a targeted manner, opening a new door for future drug delivery and treatment targeting the central nervous system
.
Paper link: https:// Open for reprinting, welcome to forward to Moments and WeChat groups
