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vasadlab.bsky.social

@vasadlab.bsky.social
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vasadlab.bsky.social @vasadlab.bsky.social · 29/05/2025
(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.
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vasadlab.bsky.social @vasadlab.bsky.social · 29/05/2025
(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.
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vasadlab.bsky.social @vasadlab.bsky.social · 29/05/2025
(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.
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vasadlab.bsky.social @vasadlab.bsky.social · 29/05/2025
(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.
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vasadlab.bsky.social @vasadlab.bsky.social · 29/05/2025
(5/9) Low oxygenation of the Aß plaques can be associated with local problems in angiogenesis www.nature.com/articles/s41...
nature.com
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 ...
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vasadlab.bsky.social @vasadlab.bsky.social · 29/05/2025
(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
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...
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vasadlab.bsky.social @vasadlab.bsky.social · 29/05/2025
(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...
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vasadlab.bsky.social @vasadlab.bsky.social · 29/05/2025
(2/9) We have characterized an unexpected cell-autonomous system to induce type-I interferon response in AD microglia.
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vasadlab.bsky.social @vasadlab.bsky.social · 29/05/2025
Really happy to see our work on Alzheimer’s disease (AD) microglia published in @science.org www.science.org/doi/10.1126/.... A great work at IBiS from Manuel Sanchez-Garcia, Nieves Lara-Ureña, Rosana March-Diaz, @alicielena.bsky.social , and all our collaborators.
science.org
Inactivation of the PHD3-FOXO3 axis blunts the type I interferon response in microglia and ameliorates Alzheimer’s disease progression
PHD3 inhibition slows down the pathology and behavioral decline of an Alzheimer’s disease mouse model.
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