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Click on the blue letter to follow us TAM receptor tyrosine kinases (RTKs) are a subfamily of protein tyrosine kinases, mainly composed of Axl, Tyro3 and Mer3 members.
Axl and Mer play a key role in macrophages: phagocytosis of apoptotic cells and as a negative feedback inhibitor of Toll-like and cytokine receptor signaling.
In the central nervous system, Tyro3 is mainly expressed on neurons, and Axl and Mer are mainly expressed on microglia.
After knocking out Axl and Mer, apoptotic cells aggregated abnormally, and the ability of microglia to migrate to the brain injury site was weakened.
On April 15, 2021, the Greg Lemke research team of the Salk Institute for Biological Research in the United States revealed that TAM-mediated phagocytosis of amyloid plaques by microglia.
Increased Axl expression on microglia in AD model mice.
During the pathogenesis of AD, microglia can be divided into plaque-associated microglia (PAM) and nonplaque-associated microglia (NPAM) according to whether they are related to amyloid plaques.
.
The researchers found that the expression of Axl on microglia in AD model mice was significantly increased.
In 9-month-old AD mice, the expression of Axl on PAM was more than 25 times higher than that of NPAM.
The Mer protein was slightly elevated in aged AD mice.
This indicates that TAM signal is involved in the pathogenesis of AD disease.
The TAM ligand Gas6 protein is almost not expressed in wild-type mice and double knockout Axl and Mer mice, but in AD model mice, the Gas6 protein associated with amyloid plaques is expressed abnormally.
Knockout of Axl or Mer alone cannot affect the abnormal expression of Gas6 protein in AD model mice, but it can completely reduce the abnormal expression of Gas6 protein after double knocking out the above two proteins.
In order to further clarify the gene expression characteristics of PAM and NPAM by TAM signal, they conducted transcriptomics analysis on 18-month-old AD model mice and subdivided microglia into 7 cell subgroups, and found that TAM signal had no effect The evolutionary characteristics of gene expression in microglia, but the effect of up-regulation of most PAM genes in disease states after inhibiting TAM signaling is weakened.
This indicates that TAM signal regulates the gene expression of microglia related to AD disease, that is to say, TAM signal may participate in the pathogenesis of AD through the bridge of microglia.
Sure enough, the researchers found that in AD model mice with double knockout of Axl or Mer, microglia were unwilling to "close" to amyloid plaques, more of them were in a resting state, and the engulfing of amyloid plaques was also reduced.
This indicates that TAM signals mediate the detection, response, and phagocytosis of microglia to amyloid lesions and other "one-stop services", and further clarifies that TAM signals specifically participate in the pathogenesis of AD disease by regulating the function of microglia.
TAM-mediated microglia phagocytosis promotes the formation of amyloid plaques.
At present, it is mainly believed that microglia phagocytosis is to inhibit the growth of plaques, but TAM signal-mediated microglia phagocytosis may not be the case.
Researchers found that the dense core of ThioflavineS-labeled senile plaques was significantly reduced in AD model mice with double knockout of Axl or Mer.
Yes, you are not mistaken.
After suppressing the TAM signal, the ability of microglia to swallow and deposit plaques is reduced, but the core part of the plate is reduced.
This means that the function of phagocytosis and deposition of plaques mediated by TAM signaling microglia instead promotes the formation of plaques.
In general, this article found that TAM signal is necessary for microglia to recognize and phagocytose amyloid plaques.
TAM-mediated microglia phagocytosis of amyloid plaques does not inhibit the formation of plaques.
It promotes the formation of plaques.[References] 1.
https://doi.
org/10.
1038/s41590-021-00913-5 The pictures in the article are all from the references
Axl and Mer play a key role in macrophages: phagocytosis of apoptotic cells and as a negative feedback inhibitor of Toll-like and cytokine receptor signaling.
In the central nervous system, Tyro3 is mainly expressed on neurons, and Axl and Mer are mainly expressed on microglia.
After knocking out Axl and Mer, apoptotic cells aggregated abnormally, and the ability of microglia to migrate to the brain injury site was weakened.
On April 15, 2021, the Greg Lemke research team of the Salk Institute for Biological Research in the United States revealed that TAM-mediated phagocytosis of amyloid plaques by microglia.
Increased Axl expression on microglia in AD model mice.
During the pathogenesis of AD, microglia can be divided into plaque-associated microglia (PAM) and nonplaque-associated microglia (NPAM) according to whether they are related to amyloid plaques.
.
The researchers found that the expression of Axl on microglia in AD model mice was significantly increased.
In 9-month-old AD mice, the expression of Axl on PAM was more than 25 times higher than that of NPAM.
The Mer protein was slightly elevated in aged AD mice.
This indicates that TAM signal is involved in the pathogenesis of AD disease.
The TAM ligand Gas6 protein is almost not expressed in wild-type mice and double knockout Axl and Mer mice, but in AD model mice, the Gas6 protein associated with amyloid plaques is expressed abnormally.
Knockout of Axl or Mer alone cannot affect the abnormal expression of Gas6 protein in AD model mice, but it can completely reduce the abnormal expression of Gas6 protein after double knocking out the above two proteins.
In order to further clarify the gene expression characteristics of PAM and NPAM by TAM signal, they conducted transcriptomics analysis on 18-month-old AD model mice and subdivided microglia into 7 cell subgroups, and found that TAM signal had no effect The evolutionary characteristics of gene expression in microglia, but the effect of up-regulation of most PAM genes in disease states after inhibiting TAM signaling is weakened.
This indicates that TAM signal regulates the gene expression of microglia related to AD disease, that is to say, TAM signal may participate in the pathogenesis of AD through the bridge of microglia.
Sure enough, the researchers found that in AD model mice with double knockout of Axl or Mer, microglia were unwilling to "close" to amyloid plaques, more of them were in a resting state, and the engulfing of amyloid plaques was also reduced.
This indicates that TAM signals mediate the detection, response, and phagocytosis of microglia to amyloid lesions and other "one-stop services", and further clarifies that TAM signals specifically participate in the pathogenesis of AD disease by regulating the function of microglia.
TAM-mediated microglia phagocytosis promotes the formation of amyloid plaques.
At present, it is mainly believed that microglia phagocytosis is to inhibit the growth of plaques, but TAM signal-mediated microglia phagocytosis may not be the case.
Researchers found that the dense core of ThioflavineS-labeled senile plaques was significantly reduced in AD model mice with double knockout of Axl or Mer.
Yes, you are not mistaken.
After suppressing the TAM signal, the ability of microglia to swallow and deposit plaques is reduced, but the core part of the plate is reduced.
This means that the function of phagocytosis and deposition of plaques mediated by TAM signaling microglia instead promotes the formation of plaques.
In general, this article found that TAM signal is necessary for microglia to recognize and phagocytose amyloid plaques.
TAM-mediated microglia phagocytosis of amyloid plaques does not inhibit the formation of plaques.
It promotes the formation of plaques.[References] 1.
https://doi.
org/10.
1038/s41590-021-00913-5 The pictures in the article are all from the references
