@vasadlab.bsky.social
(9/9) Our results show a new cell-autonomous mechanism to activate the IFN-I response in microglia. Interestingly, some PHD inhibitors are already in clinical use, and it would be interesting to see if they can improve microglial responses to Aß plaques.
May 29, 2025 at 12:49 PM
(9/9) Our results show a new cell-autonomous mechanism to activate the IFN-I response in microglia. Interestingly, some PHD inhibitors are already in clinical use, and it would be interesting to see if they can improve microglial responses to Aß plaques.
(8/9) Mechanistically, FOXO3 –a transcriptional repressor of the IFN response– stability is regulated by PHD3. Interestingly, FOXO3 has been identified in human studies as a key factor in microglial responses doi.org/10.1016/j.ce..., and we now show that FOXO3 is associated with the IFN response.
May 29, 2025 at 12:48 PM
(8/9) Mechanistically, FOXO3 –a transcriptional repressor of the IFN response– stability is regulated by PHD3. Interestingly, FOXO3 has been identified in human studies as a key factor in microglial responses doi.org/10.1016/j.ce..., and we now show that FOXO3 is associated with the IFN response.
(7/9) PHD3 deficiency correlates with a decrease in the AD microglia type-I IFN responses, decreased local Aß plaque pathology, and a rescue of the behavioral defects in AD mouse models.
May 29, 2025 at 12:46 PM
(7/9) PHD3 deficiency correlates with a decrease in the AD microglia type-I IFN responses, decreased local Aß plaque pathology, and a rescue of the behavioral defects in AD mouse models.
(6/9) We now describe a new pathway that activates type-I IFN response in microglia controlled by HIF1 and PHD3, a transcriptional target of HIF1.
May 29, 2025 at 12:45 PM
(6/9) We now describe a new pathway that activates type-I IFN response in microglia controlled by HIF1 and PHD3, a transcriptional target of HIF1.
(5/9) Low oxygenation of the Aß plaques can be associated with local problems in angiogenesis www.nature.com/articles/s41...
Non-productive angiogenesis disassembles Aß plaque-associated blood vessels - Nature Communications
Aß are extracellular deposits relevant in Alzheimer’s disease (AD). This study shows that Aß plaques are hubs of endothelial disassembly that induce non-productive angiogenesis. This process is aided ...
www.nature.com
May 29, 2025 at 12:44 PM
(5/9) Low oxygenation of the Aß plaques can be associated with local problems in angiogenesis www.nature.com/articles/s41...
(4/9) We have previously shown that Aß plaque-associated microglia have a strong HIF1-mediated response www.nature.com/articles/s43... @natmetabolism.nature.com
Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1 - Nature Aging
Microglia can help clear amyloid β plaques in the Alzheimer’s disease brain but may also become dysfunctional and can contribute to disease progression. March-Diaz et al. reveal that hypoxia, a potent...
www.nature.com
May 29, 2025 at 12:43 PM
(4/9) We have previously shown that Aß plaque-associated microglia have a strong HIF1-mediated response www.nature.com/articles/s43... @natmetabolism.nature.com
(3/9) It has been nicely demonstrated that microglial type-I IFN response is required for normal physiology and can be detrimental to the brain in chronic neurodegenerative diseases. The main controller of this response is the cGAS-STING pathway (see, for instance, www.cell.com/trends/neuro...
May 29, 2025 at 12:42 PM
(3/9) It has been nicely demonstrated that microglial type-I IFN response is required for normal physiology and can be detrimental to the brain in chronic neurodegenerative diseases. The main controller of this response is the cGAS-STING pathway (see, for instance, www.cell.com/trends/neuro...
(2/9) We have characterized an unexpected cell-autonomous system to induce type-I interferon response in AD microglia.
May 29, 2025 at 12:41 PM
(2/9) We have characterized an unexpected cell-autonomous system to induce type-I interferon response in AD microglia.