Scientists from DZNE, University Hospital Bonn (UKB) and the University of Bonn provide new evidence that preventing brain inflammation is a promising approach for the treatment of Alzheimer’s disease. Their findings, based on studies in cell culture, mice and tissue samples from patients, may contribute to the development of more effective therapies. They are published in the journal Immunity.
Alzheimer’s disease, the most common form of dementia, is associated with the deposition of proteins in the brain. The aggregation of these proteins, which are known as “amyloid-beta,” give rise to a chain of events that ultimately harm neurons and lead to their loss.
“Alzheimer’s disease involves a complex interaction of different mechanisms. One of these is neuroinflammation. That’s what we looked at in our studies. Specifically, we pharmacologically manipulated a molecular complex called the NLRP3 inflammasome. It is found in microglia, which are the immune cells of the brain,” says Dr. Róisín McManus, a DZNE research group leader, investigator at UKB’s Institute of Innate Immunity and also a member of the ImmunoSensation2 Cluster of Excellence at the University of Bonn.
Previously unknown pathways
The “NLRP3 inflammasome” is like a control switch: In Alzheimer’s disease, its activation triggers an inflammatory response that harms neurons. For this reason, researchers have been exploring ways to inactivate this molecular complex using drugs. The current results support this approach.
“It is known that inhibiting NLRP3 not only reduces neuroinflammation, but also helps microglia clear the harmful amyloid-beta deposits, a process called phagocytosis. The novelty of our findings is that they provide a better understanding of the important role that NLRP3 plays in microglia and we also unravel the mechanism behind why its inhibition is so beneficial,” says McManus.
“In our studies we have identified previously unknown signaling pathways influenced by NLRP3. In particular, we found that NLRP3 regulates how microglia use nutrients and how these act on genes that have a major impact on the function of microglia. This is very relevant for their ability to carry out phagocytosis. These findings could help in the development of therapies for dementia. In any case, our research shows that NLRP3 is a promising target for the treatment of Alzheimer’s disease.”
More information:
Róisín M. McManus et al, NLRP3-mediated glutaminolysis controls microglial phagocytosis to promote Alzheimer’s disease progression, Immunity (2025). DOI: 10.1016/j.immuni.2025.01.007
Citation:
Lab findings support concept that reducing neuroinflammation could help fight Alzheimer’s (2025, February 4)
retrieved 4 February 2025
from https://medicalxpress.com/news/2025-02-lab-concept-neuroinflammation-alzheimer.html
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part may be reproduced without the written permission. The content is provided for information purposes only.
Scientists from DZNE, University Hospital Bonn (UKB) and the University of Bonn provide new evidence that preventing brain inflammation is a promising approach for the treatment of Alzheimer’s disease. Their findings, based on studies in cell culture, mice and tissue samples from patients, may contribute to the development of more effective therapies. They are published in the journal Immunity. Alzheimer’s disease, the most common form of dementia, is associated with the deposition of proteins in the brain. The aggregation of these proteins, which are known as “amyloid-beta,” give rise to a chain of events that ultimately harm neurons and lead to their loss. “Alzheimer’s disease involves a complex interaction of different mechanisms. One of these is neuroinflammation. That’s what we looked at in our studies. Specifically, we pharmacologically manipulated a molecular complex called the NLRP3 inflammasome. It is found in microglia, which are the immune cells of the brain,” says Dr. Róisín McManus, a DZNE research group leader, investigator at UKB’s Institute of Innate Immunity and also a member of the ImmunoSensation2 Cluster of Excellence at the University of Bonn. The “NLRP3 inflammasome” is like a control switch: In Alzheimer’s disease, its activation triggers an inflammatory response that harms neurons. For this reason, researchers have been exploring ways to inactivate this molecular complex using drugs. The current results support this approach. “It is known that inhibiting NLRP3 not only reduces neuroinflammation, but also helps microglia clear the harmful amyloid-beta deposits, a process called phagocytosis. The novelty of our findings is that they provide a better understanding of the important role that NLRP3 plays in microglia and we also unravel the mechanism behind why its inhibition is so beneficial,” says McManus. “In our studies we have identified previously unknown signaling pathways influenced by NLRP3. In particular, we found that NLRP3 regulates how microglia use nutrients and how these act on genes that have a major impact on the function of microglia. This is very relevant for their ability to carry out phagocytosis. These findings could help in the development of therapies for dementia. In any case, our research shows that NLRP3 is a promising target for the treatment of Alzheimer’s disease.” More information: Citation: This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
Previously unknown pathways
Róisín M. McManus et al, NLRP3-mediated glutaminolysis controls microglial phagocytosis to promote Alzheimer’s disease progression, Immunity (2025). DOI: 10.1016/j.immuni.2025.01.007
Lab findings support concept that reducing neuroinflammation could help fight Alzheimer’s (2025, February 4)
retrieved 4 February 2025
from https://medicalxpress.com/news/2025-02-lab-concept-neuroinflammation-alzheimer.html
part may be reproduced without the written permission. The content is provided for information purposes only.
