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▎Editor of WuXi AppTec's content team Alzheimer's disease can be said to be one of the most "notorious" diseases in the medical field
.
It is notorious, on the one hand because it can swallow the memory of patients and greatly affect the quality of life; on the other hand, it is also because of its slow progress in clinical development
.
It was not until June this year that the US FDA approved the first new drug for Alzheimer's disease in 18 years
.
And even after it was approved, the controversy about it has not stopped.
.
.
Source: 123RF has so many controversies, the focus is actually on the typical pathological feature of Alzheimer's disease-amyloid deposition
.
What role does it play in Alzheimer's disease? Can removing amyloid deposits treat Alzheimer's disease? On this issue, Professor Rudolph Tanzi of Harvard Medical School has his opinion
.
This Alzheimer’s disease expert made such a vivid metaphor at the WuXi AppTec Global Forum held earlier this year: Amyloid is like a match, which can cause localized wildfires (neurofibrillary tangles), and ultimately Causes raging forest fires (neuritis and neuronal death)
.
If the entire forest is already burning, extinguishing the firewood will not help
.
Image source: Cameron Strandberg from Rocky Mountain House, Alberta, Canada, CC BY 2.
0 <https://creativecommons.
org/licenses/by/2.
0>, via Wikimedia Commons On the contrary, even if the match is still there, as long as the fire can be controlled Partially, it may actually be enough for Alzheimer's disease
.
"If it does not cause neuroinflammation, there will be no symptoms of dementia," Professor Tanzi said.
"We know that although some individuals have a lot of deposits and tangles in their brains, but there is almost no neuroinflammation, they will have no symptoms
.
" Today, the top academic journal "Nature" published an important paper online from the joint team of Professor Tanzi, which confirmed the importance and feasibility of extinguishing "forest fires"
.
This discovery has guiding significance for the development of new drugs for Alzheimer's disease
.
Why is neuroinflammation so important? Because under the action of amyloid deposition and neurofibrillary tangles, the neuroinflammation caused by the overreaction of the immune system can lead to the death of neurons, and this is the main reason for the cognitive decline of patients
.
The researchers pointed out that once neurons begin to die, they activate microglia and astrocytes in the brain
.
Under normal circumstances, these two types of cells should protect the brain and remove cellular debris
.
When they find that the abnormal neurons have died, they will mistakenly think that the brain is infected, and then clean the entire area.
Instead, they will do bad things with good intentions
.
Professor Tanzi mentioned that the number of brain cells that died of neuroinflammation was ten times that of brain cells that died of amyloid deposits and neurofibrillary tangles! In other words, even if there are amyloid deposits and neurofibrillary tangles, as long as the "forest fires" that do not cause neuroinflammation, Alzheimer's disease may be controlled
.
Image source: 123RF In order to find a way to "extinguish the fire", researchers have made further explorations
.
They found that some astrocytes secrete a molecule called IL-3
.
Previous studies have found that this molecule is related to neurodegenerative diseases, but its role has not been clarified
.
After removing IL-3 in the mouse model, the researchers found that the mice produced greater amyloid deposits and performed worse in memory than the control group
.
These results indicate that IL-3 may play a protective role in Alzheimer's disease
.
And microglia is exactly the target of IL-3
.
Whether in humans or mice, as long as Alzheimer's disease occurs, the expression of IL-3 receptors on the surface of microglia will increase
.
In contrast, this phenomenon was not observed in normal mice or human samples without dementia
.
When the researchers injected IL-3 directly into the brain of the animal model, they found that microglia began to gather near the amyloid deposits for cleaning
.
After four weeks of continuous treatment, the memory of these animals has improved, and amyloid deposits have also been reduced
.
Image source: 123RF researchers pointed out that these results indicate that in Alzheimer's disease, astrocytes release IL-3 signals, seeking help from microglia
.
Under the action of IL-3, the microglia that would have been killed indiscriminately changed their normal state
.
Not only did they not expand the impact and cause a wide range of neuroinflammation, but they also began to focus on cleaning up amyloid deposits and neurofibrillary tangles! If you apply the analogy of Professor Tanzi, IL-3 can not only prevent the immune cells in the brain from "adding fuel to the fire," it can also further extinguish the fire
.
In this way, the condition of Alzheimer's disease is expected to be brought under control
.
In summary, the study shows that astrocytes can "educate" microglia through IL-3, inhibit the neuroinflammation they cause, and further clear the typical pathology of Alzheimer's disease in the brain-amyloid Protein deposition and neurofibrillary tangles
.
This signaling pathway is also expected to provide ideas for the development of new drugs in the future, bringing new drugs for the treatment of Alzheimer's disease
.
Reference: [1] McAlpine, CS, Park, J.
, Griciuc, A.
et al.
Astrocytic interleukin-3 programs microglia and limits Alzheimer's disease.
Nature (2021).
https://doi.
org/10.
1038/s41586- 021-03734-6[2] Researchers identify signaling molecule that may help prevent Alzheimer's disease, Retrieved July 14, 2021, from https:// Controlling Alzheimer's by targeting immune signaling between brain cells, Retrieved July 14, 2021, from https://
.
It is notorious, on the one hand because it can swallow the memory of patients and greatly affect the quality of life; on the other hand, it is also because of its slow progress in clinical development
.
It was not until June this year that the US FDA approved the first new drug for Alzheimer's disease in 18 years
.
And even after it was approved, the controversy about it has not stopped.
.
.
Source: 123RF has so many controversies, the focus is actually on the typical pathological feature of Alzheimer's disease-amyloid deposition
.
What role does it play in Alzheimer's disease? Can removing amyloid deposits treat Alzheimer's disease? On this issue, Professor Rudolph Tanzi of Harvard Medical School has his opinion
.
This Alzheimer’s disease expert made such a vivid metaphor at the WuXi AppTec Global Forum held earlier this year: Amyloid is like a match, which can cause localized wildfires (neurofibrillary tangles), and ultimately Causes raging forest fires (neuritis and neuronal death)
.
If the entire forest is already burning, extinguishing the firewood will not help
.
Image source: Cameron Strandberg from Rocky Mountain House, Alberta, Canada, CC BY 2.
0 <https://creativecommons.
org/licenses/by/2.
0>, via Wikimedia Commons On the contrary, even if the match is still there, as long as the fire can be controlled Partially, it may actually be enough for Alzheimer's disease
.
"If it does not cause neuroinflammation, there will be no symptoms of dementia," Professor Tanzi said.
"We know that although some individuals have a lot of deposits and tangles in their brains, but there is almost no neuroinflammation, they will have no symptoms
.
" Today, the top academic journal "Nature" published an important paper online from the joint team of Professor Tanzi, which confirmed the importance and feasibility of extinguishing "forest fires"
.
This discovery has guiding significance for the development of new drugs for Alzheimer's disease
.
Why is neuroinflammation so important? Because under the action of amyloid deposition and neurofibrillary tangles, the neuroinflammation caused by the overreaction of the immune system can lead to the death of neurons, and this is the main reason for the cognitive decline of patients
.
The researchers pointed out that once neurons begin to die, they activate microglia and astrocytes in the brain
.
Under normal circumstances, these two types of cells should protect the brain and remove cellular debris
.
When they find that the abnormal neurons have died, they will mistakenly think that the brain is infected, and then clean the entire area.
Instead, they will do bad things with good intentions
.
Professor Tanzi mentioned that the number of brain cells that died of neuroinflammation was ten times that of brain cells that died of amyloid deposits and neurofibrillary tangles! In other words, even if there are amyloid deposits and neurofibrillary tangles, as long as the "forest fires" that do not cause neuroinflammation, Alzheimer's disease may be controlled
.
Image source: 123RF In order to find a way to "extinguish the fire", researchers have made further explorations
.
They found that some astrocytes secrete a molecule called IL-3
.
Previous studies have found that this molecule is related to neurodegenerative diseases, but its role has not been clarified
.
After removing IL-3 in the mouse model, the researchers found that the mice produced greater amyloid deposits and performed worse in memory than the control group
.
These results indicate that IL-3 may play a protective role in Alzheimer's disease
.
And microglia is exactly the target of IL-3
.
Whether in humans or mice, as long as Alzheimer's disease occurs, the expression of IL-3 receptors on the surface of microglia will increase
.
In contrast, this phenomenon was not observed in normal mice or human samples without dementia
.
When the researchers injected IL-3 directly into the brain of the animal model, they found that microglia began to gather near the amyloid deposits for cleaning
.
After four weeks of continuous treatment, the memory of these animals has improved, and amyloid deposits have also been reduced
.
Image source: 123RF researchers pointed out that these results indicate that in Alzheimer's disease, astrocytes release IL-3 signals, seeking help from microglia
.
Under the action of IL-3, the microglia that would have been killed indiscriminately changed their normal state
.
Not only did they not expand the impact and cause a wide range of neuroinflammation, but they also began to focus on cleaning up amyloid deposits and neurofibrillary tangles! If you apply the analogy of Professor Tanzi, IL-3 can not only prevent the immune cells in the brain from "adding fuel to the fire," it can also further extinguish the fire
.
In this way, the condition of Alzheimer's disease is expected to be brought under control
.
In summary, the study shows that astrocytes can "educate" microglia through IL-3, inhibit the neuroinflammation they cause, and further clear the typical pathology of Alzheimer's disease in the brain-amyloid Protein deposition and neurofibrillary tangles
.
This signaling pathway is also expected to provide ideas for the development of new drugs in the future, bringing new drugs for the treatment of Alzheimer's disease
.
Reference: [1] McAlpine, CS, Park, J.
, Griciuc, A.
et al.
Astrocytic interleukin-3 programs microglia and limits Alzheimer's disease.
Nature (2021).
https://doi.
org/10.
1038/s41586- 021-03734-6[2] Researchers identify signaling molecule that may help prevent Alzheimer's disease, Retrieved July 14, 2021, from https:// Controlling Alzheimer's by targeting immune signaling between brain cells, Retrieved July 14, 2021, from https://
